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The white-tufted marmoset is a small, nonhuman primate that is rapidly gaining popularity as a model organism, especially for neuroscience research. To date, little work in the alcohol research field has utilized the marmoset. As a step toward establishing the marmoset as a research model for alcohol experimentation, a series of exploratory studies were undertaken to characterize ethanol drinking behavior. A voluntary drinking paradigm was established whereby the common marmoset would consume pharmacologically relevant amounts of ethanol. To facilitate ethanol consumption, ethanol was mixed with a marshmallow flavored solution (hereafter called marshmallow juice) to mask the presumed adverse taste of ethanol. Using marshmallow juice flavored solutions, marmosets readily consumed ethanol up to 1 g/kg during 10 min binge-like drinking sessions or up to 5 g/kg during ∼4 h drinking sessions. Consumption of 1.0–1.5 g/kg during a 30 min session resulted in blood ethanol concentrations of 49–73 mg/dl, which are predicted to be pharmacologically relevant. In animals that were stably consuming ethanol in marshmallow juice, gradually reducing the concentration of the marshmallow juice flavoring resulted in markedly reduced ethanol consumption. Lastly, when offered a choice between ethanol in marshmallow juice and marshmallow juice alone, marmosets displayed a very strong preference for the marshmallow juice solution without ethanol. From these studies, it is concluded that marmosets will voluntarily consume ethanol if the taste is masked with a sweet solution such as marshmallow juice. These studies represent the first report of alcohol consumption and preference in the white-tufted marmoset. • The white-tufted marmoset is rapidly gaining popularity as a model organism, especially for neuroscience research. • To date, the marmoset has not been extensively studied by alcohol researchers. • Marmosets will readily consume low doses of ethanol if the presumed adverse taste is masked by a sweet flavoring. [ABSTRACT FROM AUTHOR]

Alcohol use disorder (AUD) is a major public health concern that despite its prevalence, lacks a widely-effective treatment due to the complexity of AUD pathology. AUD is highly comorbid with other psychiatric conditions including anxiety and mood disorders, however it is unclear how these disorders influence each other. The underlying etiology of these comorbidities is difficult to decipher and factors including sex, stress, and the environment further complicate both diagnosis and treatment strategies. To understand more about this bidirectional relationship between AUD and comorbid psychiatric disorders, we ran male and female C57Bl/6j mice through baseline behavioral testing followed by intermittent access-two bottle choice (IA-2BC) drinking. We found no sex differences in basal anxiety-like or depressive-like behavior, however females displayed enhanced motivated feeding behavior. Females consumed more ethanol than males, at both 1hr and 24hr timepoints. Basal affective state did not predict subsequent ethanol intake in either sex, however exploratory behavior was positively correlated with drinking in males but not females. We then re-assessed negative affect behavior following chronic ethanol drinking to determine if drinking impacted subsequent affective behavior and found no relationship between ethanol intake and affective state in males or females. We also examined how chronic ethanol drinking affected central amygdala (CeA) and basolateral amygdala (BLA) neuronal activity in males and females. Ethanol-drinking females had a decrease in CeA neuronal activity, driven by reduced activity in the lateral (CeA l) sub-region, while in males there was no significant difference in CeA activity compared to water controls. Neither males or females had a significant change in BLA neuronal activity following chronic ethanol drinking. Collectively, these results demonstrate sex differences in basal motivated behavior, drinking behavior, and subregion-specific amygdala neuronal activity following chronic ethanol drinking which may inform the sex differences seen in patients diagnosed with AUD and comorbid conditions. • There were no basal sex differences in affective behavior. • Basal affective behavior did not determine future ethanol intake. • Chronic ethanol drinking did not alter subsequent affective behavior. • CeA activity was reduced in ethanol-exposed females compared to water controls. • BLA activity did not differ between male and female ethanol and water groups. [ABSTRACT FROM AUTHOR]

Alcohol abuse (AA) has s high prevalence, affecting 10 to 15 million Americans. While AA was demonstrated to negatively impact cardiovascular health, limited evidence from existing studies presents conflicting findings regarding the effects of AA on coronary artery bypass grafting (CABG) outcomes. This study aimed to compare the in-hospital outcomes after CABG between AA and non-AA patients. Patients who underwent CABG were identified in National Inpatient Sample from Q4 2015–2020. Exclusion criteria included age<18 years and concomitant procedures. A 1:3 propensity-score matching was used to address differences in demographics, socioeconomic status, primary payer status, hospital characteristics, comorbidities, and transfer/admission status between AA and non-AA patients. In-hospital outcomes after CABG were examined. There were 5694 (3.39%) AA patients who underwent CABG. After matching, 17,315 from 162,488 non-AA patients were matched to all AA patients. AA and non-AA patients had comparable mortality (1.64% vs 1.55%, p = 0.67) and MACE (2.46% vs 2.56%, p = 0.73). However, AA patients had higher cardiogenic shock (8.31% vs 7.43%, p = 0.03), mechanical ventilation (11.51% vs 7.96%, p < 0.01), hemorrhage/hematoma (57.49% vs 54.75%, p < 0.01), superficial (0.99% vs 0.61%, p < 0.01) and deep wound complications (0.37% vs 0.18%, p = 0.02), reopen surgery for bleeding control (0.92% vs 0.63%, p = 0.03), transfer out (21.00% vs 16.38%, p < 0.01), longer time from admission to operation (p < 0.01), longer length of stay (p < 0.01), and higher hospital charge (p < 0.01). While AA was not found to be linked with in-hospital mortality or MACE after CABG, it was independently associated with postoperative complications. These findings could enhance preoperative risk stratification for AA patients and inform postoperative management following CABG. • This study compared in-hospital CABG outcomes between patients with and without alcohol abuse in National Inpatient Sample. • While alcohol abuse was not linked with in-hospital mortality after CABG, it was independently associated with complications. • These findings could enhance preoperative risk stratification for alcohol abuse patients and inform postoperative management. [ABSTRACT FROM AUTHOR]

Alcohol consumption is not uncommon among people with HIV (PWH) and may exacerbate HIV-induced intestinal damage, and further lead to dysbiosis and increased intestinal permeability. This study aimed to determine the changes in the fecal microbiota and its association with alcohol consumption in HIV-infected patients. A cross-sectional survey was conducted between November 2021 and May 2022, and 93 participants were recruited. To investigate the alterations of alcohol misuse on fecal microbiology in HIV-infected individuals, we performed 16s rDNA gene sequencing on fecal samples from the low-to-moderate drinking (n = 21) and non-drinking (n = 72) groups. Comparison between groups using alpha and beta diversity showed that the diversity of stool microbiota in the low-to-moderate drinking group did not differ from that of the non-drinking group (all p > 0.05). The Linear discriminant Analysis effect size (LEfSe) algorithm was used to determine the bacterial taxa associated with alcohol consumption, and the results showed altered fecal bacterial composition in HIV-infected patients who consumed alcohol; Coprobacillus , Pseudobutyrivibrio , and Peptostreptococcaceae were enriched, and Pasteurellaceae and Xanthomonadaceae were depleted. In addition, by using the Kyoto Encyclopedia of Genes and Genomes (KEGG), functional microbiome features were also found to be altered in the low-to-moderate drinking group compared to the control group, showing a reduction in metabolic pathways (p = 0.036) and cardiovascular disease pathways (p = 0.006). Low-to-moderate drinking will change the composition, metabolism, and cardiovascular disease pathways of the gut microbiota of HIV-infected patients. • Alcohol use and gut microbial composition in PWH is an important area of research. • Alcohol consumption alters the composition of the gut microflora in PWH. • Alcohol consumption reduces metabolic pathways and cardiovascular disease pathways. [ABSTRACT FROM AUTHOR]

Ceftriaxone is an antibiotic that increases central nervous system (CNS) protein expression of the glutamate transporters GLT-1 and xCT and ameliorates pathological behaviors in rodent models of neurological disease and substance use disorder. However, little ceftriaxone passes through the blood–brain barrier, the CNS binding partner of ceftriaxone is unknown, and ceftriaxone does not consistently upregulate GLT-1 and xCT in cell culture. Ceftriaxone alters the gut microbiome composition in rodents and humans, and the microbiome–gut–brain axis regulates drug-seeking. Thus, here we test the hypothesis that ceftriaxone reduces alcohol intake while ameliorating alcohol-induced disruption of the gut microbiome composition. Male and female Sprague–Dawley rats received intermittent access to alcohol (IAA) while controls received access to only water. Following 17 IAA sessions, ceftriaxone/vehicle treatment was given for 5 days. Analysis of the gut microbiome composition was assessed by 16S rRNA gene amplicon sequencing conducted on fecal pellets collected prior to and after alcohol consumption and following ceftriaxone treatment. Male rats displayed escalated alcohol intake and preference over the course of the 17 sessions; however, total alcohol intake did not differ between the sexes. Ceftriaxone reduced alcohol intake and preference in male and female rats. While alcohol affected a diverse set of amplicon sequencing variants (ASV), ceftriaxone markedly reduced the diversity of microbial communities reflected by a blooming of the Enterococcaceae family. The remaining effects of ceftriaxone, however, encompassed families both affected and unaffected by prior alcohol drinking and highlight the Ruminococcaceae and Muribaculaceae families as bidirectionally modulated by alcohol and ceftriaxone. Altogether, our study confirms that ceftriaxone reduces alcohol intake in rats and partially reverses alcohol-induced dysbiosis. • Total amount of alcohol intake did not differ by sex. • Ceftriaxone reduced alcohol intake and preference in male and female rats. • Ceftriaxone markedly reduced the diversity of microbial communities. • Ceftriaxone partially reverses alcohol-induced dysbiosis. [ABSTRACT FROM AUTHOR]

Research confirms that stress is associated with alcohol drinking and relapse in males and females and that there are sex differences in the alcohol-related adaptations of stress pathways. The predator stress (PS) model of traumatic stress produces an increase in alcohol drinking or self-administration in a subpopulation of rodents, so it is utilized as an animal model of comorbid alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD). Previous work determined that sensitivity to PS-enhanced drinking produced sex differences in proteins related to stress-regulating systems in the medial prefrontal cortex and hippocampus. The present studies examined whether male and female C57BL/6J mice differ in sensitivity to the ability of the corticotropin releasing factor receptor 1 antagonist CP-376395 to decrease PS-enhanced drinking. In control studies, CP-376395 doses of 5, 10, and 20 mg/kg dose-dependently decreased 4-h ethanol drinking. Next, CP-376395 doses of 5 and 10 mg/kg were tested for effects on ethanol drinking in mice with differential sensitivity to PS-enhanced drinking. Subgroups of "Sensitive" and "Resilient" male and female mice were identified based on changes in ethanol intake in an unrestricted-access ethanol-drinking procedure following four exposures to PS (dirty rat bedding). During the first 2 h post-injection of CP-376395, both doses significantly decreased ethanol licks versus vehicle in the females, with no significant interaction between subgroups, whereas the 10 mg/kg dose significantly decreased ethanol licks versus vehicle in the "Resilient" males. Thus, sensitivity to the suppressive effect of CP-376395 on stress-induced ethanol intake was greater in females versus males, whereas sensitivity and resilience to PS-enhanced drinking produced differential sensitivity to the ability of CP-376395 to decrease ethanol drinking only in male mice. Our results argue against greater efficacy of CRF-R1's ability to decrease ethanol intake in subjects with traumatic stress-enhanced ethanol drinking. • CRF-R1 antagonist CP-376395 decreased alcohol intake in control male and female mice. • This decrease was less alcohol-selective in male than in female mice. • CP-376395 decreased alcohol intake in female mice following repeated predator stress. • CP-376395 decreased such intake only in males resistant to stress-enhanced drinking. • Predator stress-enhanced alcohol drinking does not increase CRF-R1 sensitivity. [ABSTRACT FROM AUTHOR]

HIV transmission remains a significant health concern for men who have sex with men (MSM) in the United States. Heavy episodic drinking (HED) is related to increased rates of condomless anal intercourse (CAI) among MSM, though evidence suggests that this association may vary by individual difference factors. The present secondary analysis tested whether sexual alcohol expectancies (SAEs) moderate the associations between frequency of HED and anal intercourse (AI) with and without a condom among moderate-to-heavy drinking HIV- MSM. Two hundred and forty-eight moderate-to-heavy drinking MSM completed self-report questionnaires including the Sexual Behavior Questionnaire, the Modified Daily Drinking Questionnaire, and the Sexual Alcohol Expectancies Questionnaire. Negative binomial regressions indicated that SAEs moderated the association between frequency of HED and AI with a condom, but not between the frequency of HED and condomless AI (CAI). These results suggest that stronger SAEs play a role in alcohol-related sexual behavior among MSM, but do not provide evidence that SAEs are associated with increased risk for HIV transmission through CAI. • Expectancies moderate the drinking-frequency and anal-sex frequency relation. • Expectancies do not moderate relation of drinking frequency and condomless anal sex. • Expectancies related to increased riskiness are the strongest moderators. [ABSTRACT FROM AUTHOR]

Alcohol consumption is a significant risk factor for several types of injuries and trauma recidivism and remains an important public health concern worldwide. We aimed to describe the implementation of mandatory alcohol screening and the AUDIT tool among trauma patients admitted to a level 1 trauma center in a country with a partial ban on alcohol consumption. This was a retrospective analysis of trauma patients (>12 years old) who required hospital admission and underwent blood alcohol concentration (BAC) screening between 2014 and 2019. This was achieved via an enzymatic method using alcohol dehydrogenase for ethanol detection in the plasma and serum samples. Trauma patients with a BAC <2.2 mmol/L were referred to as "negative", and BAC >2.2 mmol/L was referred to as "BAC positive". A comparative analysis was performed between the two BAC groups. Alcohol Screening, Brief Intervention, Referral for Treatment [ASBIRT] program, and AUDIT were applied. A total of 7326 BAC screening tests were performed on 7284 patients during the study period. With slight variation over the years, the compliance rate was 77% (70.4%–85.3%), and the test positivity rate was 10% (8.6%–12.5%). There were 42 repeated admissions, of which seven patients were BAC positive at every admission. Young age and non-Arab patients were more likely to test positive, and the main mechanism of injury (MOI) was road traffic-related trauma (p < 0.05). Assault and self-inflicted injuries were significantly higher in BAC-positive patients than in BAC-negative patients (18% vs. 4% and 2.7% vs. 1.3%, respectively; p = 0.001). The injury severity score (ISS) and mortality rate were comparable between the study groups. Patients with a positive BAC were significantly more likely to undergo pan-CT scan in the emergency department, intubation, and exploratory laparotomy than those with a negative BAC. In patients who sustained injuries due to assault, all-terrain vehicles, or motorcycle crashes, there was a significant association between the positivity of BAC tests and the patient's ISS. Despite improvements in BAC screening in trauma admissions over the years, almost 20% of cases were missed. Although the mortality rates were comparable, alcohol consumption burdens resources in terms of excess imaging, intubation, open abdominal surgery, and possible disability. Further studies are needed to understand the key obstacles and challenges to achieving optimum compliance for screening in trauma settings. • Alcohol consumption is a significant risk factor for several types of injury and trauma recidivism. • In Qatar, there is a partial ban on alcohol use and a zero-tolerance policy for driving under the influence of alcohol. • There is a newly implemented mandatory alcohol screening protocol and auditing in the national trauma center since 10 years. • The compliance rate for BAC screening and psychiatry referral in trauma patients has improved over the study period. • Although mortality was comparable, alcohol consumption poses a burden on the hospital resources. [ABSTRACT FROM AUTHOR]

Many drugs of abuse, including alcohol, disrupt long-term synaptic depression (LTD) at dorsal striatal glutamate synapses. This disruption is common to many forms of LTD that are mediated by G protein coupled receptors (GPCRs) that signal through the inhibitory G i/o class of G proteins. A loss of LTD is thought to mediate behavioral changes associated with the development of substance use disorders. We have previously shown in multiple studies that LTD mediated by the G i/o -coupled mu opioid receptor is disrupted by in vivo opioid and alcohol exposure in adolescent and adult mice. One of our previous studies suggested that LTD mediated by delta and kappa opioid receptors was resistant to the LTD-disrupting properties of in vivo opioid exposure. We hypothesized that delta and kappa opioid receptor-mediated LTD would be exceptions to the generalizable observation that forms of dorsal striatal G i/o -coupled receptor LTD are disrupted by drugs of abuse. Specifically, we predicted that these forms of LTD would be resistant to the deleterious effects of alcohol consumption, just as they were resistant to opioid exposure. Indeed, in adult male mice that drank alcohol for 3 weeks, delta and kappa opioid receptor-mediated LTD at glutamatergic inputs to direct pathway and indirect pathway medium spiny neurons in the dorsolateral striatum was unaffected by alcohol. These data demonstrate that alcohol effects on GPCR-mediated LTD are not generalizable across all types of G i/o -coupled GPCRs. • Kappa and delta opioid receptor long-term depression occur at glutamate inputs to both subtypes of medium spiny neurons in dorsolateral striatum. • Neither kappa or delta opioid receptor long-term synaptic depression is sensitive to previous alcohol drinking. • Alcohol effects on opioid long-term depression are not generalizable across all subtypes of opioid receptors. [ABSTRACT FROM AUTHOR]

The aim of this qualitative study, nested in a randomized controlled trial, was to assess the mechanisms of the effects in both arms through examining perceptions of the participants about changes in their drinking behavior and their attributions for any perceived changes. We conducted semi-structured interviews with a sub-sample of trial participants. We used thematic analysis to analyze the data. Self-perceived change, mostly positive, was reported regardless of the objectively measured remission status. Participating in the trial itself was a major catalyst for change. Participants in both arms used a variety of similar strategies to make these changes; additionally, for those who received the intervention, both the style of the counselor (for example, the non-judgmental stance) as well as specific elements of the intervention were seen to influence change in drinking behavior. Absence of self-reported change was relatively uncommon and primarily related to the felt need for alcohol (e.g., drinking was perceived to be necessary to maintain good health), or the belief that one did not need to or want to change. Experiences of participating in a trial, the counselor style, and specific elements of a brief psychological treatment, play a role in influencing change in harmful drinking behaviors. • Positive change may be reported in the absence of objectively measured remission. • Trial procedures themselves become a major catalyst for modifying drinking behaviors. • Counselor style and specific elements of the intervention influence change in drinking. [ABSTRACT FROM AUTHOR]

Alcohol and nicotine are the two most important risk factors of chronic pancreatitis, and they often occur together. It is still unclear how much they influence the severity of the disease and which of the two addictions should be treated with priority. We performed a single-center, retrospective, cross-sectional study in a mixed medicosurgical cohort of 870 patients diagnosed with chronic pancreatitis (CP). We analyzed the impact of the drinking pattern and abstinence for alcohol and nicotine on the course of the disease. Patients with alcoholic CP were subdivided into 1) patients with "life-time drinking history" (LTDH), 2) "current drinkers" with current alcohol abuse without signs of LTDH, and 3) "former drinkers" who stopped or reduced alcohol intake dramatically. Compared to patients with LTDH, "former drinkers" had a lower rate of exocrine insufficiency (29% vs. 59%) and pseudocysts (33% vs. 49%), were more often relapse-free (37% vs. 5%), and had less abdominal pain. There was no correlation detected between the quantity of alcohol consumption and the severity or progression of the disease. Regarding nicotine, 29 pack-years are the threshold for developing the early stage of CP. Under nicotine abstinence, only slightly more patients were relapse-free (37% vs. 22%). In contrast, the cumulative amount of nicotine consumed correlated with overall disease severity and the development of pseudocysts. The need for surgery was increased, with odds ratios of 1.8, for both alcohol and nicotine abuse. Alcohol cessation in chronic pancreatitis reduces exocrine insufficiency, abdominal pain, and local complications. The effect of nicotine cessation is less pronounced in our cohort. However, nicotine abuse represents an important factor for the development of the disease. • Alcohol cessation results in a lower rate of exocrine insufficiency, pseudocysts, and acute pancreatitis episodes. • The drinking pattern, but not the absolute amount of alcohol, correlates with the disease severity. • We were able to identify a threshold of 29 pack-years for the development of chronic pancreatitis. • Smoking cessation only reduced the relapse frequency of acute pancreatitis episodes without affecting the disease severity. [ABSTRACT FROM AUTHOR]

Impulsivity and substance-related outcomes share a complex relationship, as various facets of impulsivity exhibit distinct associations with different drug-related outcomes. This study examines the associations between frequency and quantity of alcohol and marijuana use with impulsivity traits, psychological distress, and the utilization of emotion regulation strategies. A survey asked Argentinian citizens (n = 1507, 356 men) about frequency and quantity of alcohol or marijuana use on each day of a typical week, as well as anxiety, stress, and depression symptoms (DASS-21), impulsivity-like traits (UPPS-P), and emotion regulation strategies (ERQ). The 2-month prevalence of alcohol or marijuana use was 80.1%, and 27.2%, respectively. Premeditation was significantly (p < 0.05) and negatively associated with both frequency and quantity of alcohol consumed, whereas negative and positive urgency were positively and significantly (p < 0.05) associated with quantity of alcohol or marijuana use, respectively. Greater depression symptoms predicted greater quantity of alcohol use, whereas lower emotional suppression or lower cognitive reappraisal were significantly (p < 0.05) associated with a greater frequency of alcohol or marijuana use. Sensation seeking was significantly (p < 0.05) and positively associated with frequency of marijuana use. Individuals with higher levels of impulsivity-like traits, higher levels of depression, or lower use of emotional regulation abilities appeared to be at a higher risk of alcohol or marijuana use. In this sample, the use of alcohol (though not marijuana) seems to fit a negative reinforcement pathway. The study suggests that individuals with risk factors for drug misuse could benefit from interventions aimed at enhancing emotion regulation. • We assessed alcohol and marijuana use in 1507 Argentinian citizens. • Psychological distress, impulsivity, and use of emotion regulation were measured. • Negative urgency and depression predicted quantity, but not frequency, of alcohol use. • Sensation seeking predicted frequency, but not quantity, of marijuana use. • Quantity of alcohol consumed seemed to fit a negative reinforcement pathway. [ABSTRACT FROM AUTHOR]

Alcohol use is associated with an increased incidence of negative health outcomes in burn patients due to biological mechanisms that include a dysregulated inflammatory response and increased intestinal permeability. This study used phosphatidylethanol (PEth) in blood, a direct biomarker of recent alcohol use, to investigate associations between a recent history of alcohol use and the fecal microbiota, short chain fatty acids, and inflammatory markers in the first week after a burn injury for nineteen participants. Burn patients were grouped according to PEth levels of low or high and differences in the overall fecal microbial community were observed between these cohorts. Two genera that contributed to the differences and had higher relative abundance in the low PEth burn patient group were Akkermansia , a mucin degrading bacteria that improves intestinal barrier function, and Bacteroides , a potentially anti-inflammatory bacteria. There was no statistically significant difference between levels of short chain fatty acids or intestinal permeability across the two groups. To our knowledge, this study represents the first report to evaluate the effects of burn injury and recent alcohol use on early post burn microbiota dysbiosis, inflammatory response, and levels of short chain fatty acids. Future studies in this field are warranted to better understand the factors associated with negative health outcomes and develop interventional trials. • Recent history of alcohol use prior to burn injury has an impact on fecal microbiota. • Increased evidence of burn injured alcohol users having lower Akkermansia and Bacteroides. • Short chain fatty acid and intestinal permeability marker concentrations not correlated to alcohol use in burn patients. • Several genera were significantly different for butyrate between the two groups of burn patients who are alcohol users. [ABSTRACT FROM AUTHOR]

On December 8th 2023, the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the University of Colorado Anschutz Medical Campus in Aurora, Colorado. The 2023 meeting focused broadly on how acute and chronic alcohol exposure leads to immune dysregulation, and how this contributes to damage in multiple tissues and organs. These include impaired lung immunity, intestinal dysfunction, autoimmunity, the gut-Central Nervous System (CNS) axis, and end-organ damage. In addition, diverse areas of alcohol research covered multiple pathways behind alcohol-induced cellular dysfunction, including inflammasome activation, changes in miRNA expression, mitochondrial metabolism, gene regulation, and transcriptomics. Finally, the work presented at this meeting highlighted novel biomarkers and therapeutic interventions for patients suffering from alcohol-induced organ damage. • Alcohol increases bioactive lipids and impacts immune cell heterogeneity. • Albumin, RvD1, PIO treatment may alleviate alcohol-related tissue inflammation. • Intrinsic immune signaling by IRF3 and C5 induce ethanol-related pathologies. • The gut and associated dysbiosis by alcohol impacts autoimmunity and lung infection. • Alcohol use may result in excessive inflammation post-mild traumatic brain injury. [ABSTRACT FROM AUTHOR]

There is no intervention that quickly reduces a person's blood alcohol content (BAC). "Sober up before you drive" may prevent road traffic injury (RTI) caused by alcohol consumption. The aim of this study was to analyze the risk of RTI on an hourly basis (1–6 h) after the last drink and the determinants of this risk. This was a case-crossover study of alcohol consumption among 430 patients who suffered an RTI and arrived at an emergency department in a large hospital in Mexico City from January to April 2022. Of the 430 patients studied, 46 reported drinking within 1 h before the RTI, for a risk ratio (RR) of 7.7 (95% CI [5.6, 10.4]). This RR decreased to 2.2 (95% CI [1.3, 3.7]) for the 12 patients drinking in the second hour before the RTI and was null for those drinking earlier (p ≤ 0.001 for the trend). The induction time was 3 h among those with higher BAC and intoxication levels. The RR for an RTI decreases 71% from the first to second hour from the last drink and 32% from the second to third hour. This decrease was similar among those intoxicated and those with increased BACs. In multiple regression models, higher levels of intoxication and higher BACs remained associated with higher RRs. People should avoid driving after drinking. Waiting to drive, walking, or riding after drinking reduces the risk of an RTI, especially for people with higher BAC and intoxication levels. • The risk of TRI was higher 1 h after the last drink and decreased thereafter. • Risk was similar for drivers, pedestrians, and passengers. • The induction time was 1–2 h, extended for those with high BAC or intoxication. • Elevated risk depended on BAC at hospital entry and feeling intoxicated at injury. [ABSTRACT FROM AUTHOR]

Sexual minorities (SMs; e.g., lesbian, gay, bisexual, and other non-heterosexual individuals) are more likely to be current alcohol drinkers than their heterosexual peers while separately experiencing elevated inflammation. Yet, little research has assessed the association between alcohol use and inflammation among subgroups of SMs, let alone potential differences among people with multiple marginal identities (e.g., race/ethnicity and sexual identity). Data came from the National Health and Nutrition Survey 2015–2016. Survey-weighted multivariable linear regression analysis was used to assess the relationship between alcohol use categories, heavy episodic drinking, and log-CRP (C-reactive protein). Models were stratified by sexual identity to determine whether associations between alcohol use and inflammation or between race/ethnicity and inflammation differed by sexual identity. Among 3220 participants, 1000 (36.8%) reported light alcohol use, 870 (32.0%) reported moderate use, and 483 (17.8%) reported heavy use. Mean raw CRP was 4.1 mg/L (SD = 8.1). The association between race/ethnicity and CRP differed in stratified relative to non-stratified models with key differences in CRP among individuals with multiple marginalized identities. We also observed that while the "classic" J-shaped relationship between alcohol use and systemic inflammation persists among heterosexuals in this sample, it does not hold among subgroups of sexual minorities. In particular, bisexuals who report heavy alcohol use, compared to non-users, experience significantly elevated CRP. Finally, we did not observe any association between heavy episodic drinking and CRP among subgroups of sexual minorities. Future studies assessing alcohol and biomarker data need to strive to include subgroups of sexual minorities and people with multiple marginal identities to better target behavioral and biomedical interventions aimed at reducing health disparities. • CRP differed based on intersecting identities of sexual minority status and race/ethnicity. • The alcohol use and inflammation association differs based on intersecting identities. • The classic J-shaped relationship does not appear to hold for sexual minorities. • There was no association between heavy episodic drinking and CRP among sexual minorities. [ABSTRACT FROM AUTHOR]

Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study was to investigate peripheral nerve damage, and to correlate clinical, epidemiological and neurophysiological findings, in patients diagnosed with Alcohol Use Disorder (AUD). Ninety alcohol-dependent subjects on inpatient basis were enrolled in this prospective study over a 3-year period. Every subject was assessed by the Neuropathy Symptoms Score (NSS) questionnaire and the Neuropathy Impairment Score (NIS) clinical examination grading scale, followed by Nerve Conduction Studies, Quantitative Sensory Testing and Sympathetic Skin Response (SSR) testing. Peripheral neuropathy was diagnosed in 54 subjects (60%), by abnormal neurophysiological tests and presence of clinical signs or symptoms. Among them, pure large fiber neuropathy (LFN) was found in 18 subjects, pure small fiber neuropathy (SFN) in 12 subjects, and both large and small fiber neuropathy was diagnosed in 24 subjects. Using linear regression, we found that higher NSS and NIS scores correlated with lower amplitudes of the sural sensory nerve action potential and of the SSR. We also found a significant longer duration of alcohol abuse in subjects with neuropathy, using Student's t-test (p = 0.024). Additionally, applying NIS abnormal cut-off score ≥4, using ROC analysis, we predicted the majority of subjects with LFN, confirming 95.23% sensitivity and 93.75% specificity. Our study confirmed that peripheral neuropathy involving large and small nerve fibers, with a symmetrical length-dependent pattern, is common between patients with AUD and related to the duration of the disorder. We suggest that NSS and NIS scales could be used for the assessment of neuropathy in clinical practice, when the essential neurophysiological testing is not available. • Peripheral neuropathy with feet affected before hands is common in patients with alcohol use disorder. • Alcohol-related peripheral neuropathy correlates with the duration of the abuse. • Neurophysiological testing is essential for the diagnosis of alcohol-related peripheral neuropathy. • Clinical neuropathy scales could be useful for assessing alcohol-related peripheral neuropathy. • Proposed cut-off scores are ≥4 for Neuropathy Impairment Score and ≥1 for Neuropathy Symptoms Score. [ABSTRACT FROM AUTHOR]

Large population-based studies have suggested a link between increased alcohol use and reduced pain. In addition, these studies suggest that higher levels of pain intensity are associated with an increase in alcohol consumption and rates of hazardous drinking which potentiates the risk of developing alcohol use disorders (AUD). The mechanisms and determinants of the alcohol–pain interaction can be studied in preclinical studies. The overall goal of this study is to use animal models to explore the impact of acute postoperative pain on alcohol intake. To achieve this, we characterized the timeline and levels of alcohol intake and preference in mice after laparotomy in the 2-bottle choice paradigm. Our results show that laparotomy surgery increased alcohol intake and preference in male mice but not females in the 2-bottle choice and 3-bottle choice assays. In addition, ketoprofen administration blocked the increase in alcohol consumption in male mice after laparotomy. We also found that changes in alcohol initial sensitivity and acute functional tolerance, using loss of righting reflex (LORR) response, occur after surgery in mice. Taken together, these findings suggests that sex, pain and alcohol sensitivity-related factors may modulate the relationship between alcohol consumption and pain. • Acute laparotomy postoperative pain increases alcohol intake in male but not female mice. • Ketoprofen administration blocked the increase in alcohol consumption in mice after laparotomy. • Alcohol initial sensitivity and acute functional tolerance occur after surgery in mice. [ABSTRACT FROM AUTHOR]

While DNA serves as the fundamental genetic blueprint for an organism, it is not a static entity. Gene expression, the process by which genetic information is utilized to create functional products like proteins, can be modulated by a diverse range of environmental factors. Epigenetic mechanisms, including DNA methylation, histone modification, and microRNAs, play a pivotal role in mediating the intricate interplay between the environment and gene expression. Intriguingly, alterations in the epigenome have the potential to be inherited across generations. Alcohol use disorder (AUD) poses significant health issues worldwide. Alcohol has the capability to induce changes in the epigenome, which can be inherited by offspring, thus impacting them even in the absence of direct alcohol exposure. This review delves into the impact of alcohol on the epigenome, examining how its effects vary based on factors such as the age of exposure (adolescence or adulthood), the duration of exposure (chronic or acute), and the specific sample collected (brain, blood, or sperm). The literature underscores that alcohol exposure can elicit diverse effects on the epigenome during different life stages. Furthermore, compelling evidence from human and animal studies demonstrates that alcohol induces alterations in epigenome content, affecting both the brain and blood. Notably, rodent studies suggest that these epigenetic changes can result in lasting phenotype alterations that extend across at least two generations. In conclusion, the comprehensive literature analysis supports the notion that alcohol exposure induces lasting epigenetic alterations, influencing the behavior and health of future generations. This knowledge emphasizes the significance of addressing the potential transgenerational effects of alcohol and highlights the importance of preventive measures to minimize the adverse impact on offspring. [Display omitted] • Chronic ethanol consumption alters the epigenome, such as DNA methylation. • Ethanol consumption before gestation affects offspring. • Ethanol alters behavior in offspring who were not prenatally exposed. [ABSTRACT FROM AUTHOR]

The central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) are reciprocally connected nodes of the extended amygdala thought to play an important role in alcohol consumption. Studies of immediate-early genes indicate that BNST and CeA are acutely activated following alcohol drinking and may signal alcohol reward in nondependent drinkers, while stress signaling in the extended amygdala following chronic alcohol exposure drives increased drinking via negative reinforcement. However, the temporal dynamics of neuronal activation in these regions during drinking behavior are poorly understood. In this study, we used fiber photometry and the genetically encoded calcium sensor GCaMP6s to assess acute changes in neuronal activity during alcohol consumption in BNST and CeA before and after a chronic drinking paradigm. Activity was examined in the pan-neuronal population and separately in dynorphinergic neurons. BNST and CeA showed increased pan-neuronal activity during acute consumption of alcohol and other fluid tastants of positive and negative valence, as well as highly palatable chow. Responses were greatest during initial consummatory bouts and decreased in amplitude with repeated consumption of the same tastant, suggesting modulation by stimulus novelty. Dynorphin neurons showed similar consumption-associated calcium increases in both regions. Following three weeks of continuous alcohol access (CA), calcium increases in dynorphin neurons during drinking were maintained, but pan-neuronal activity and BNST-CeA coherence were altered in a sex-specific manner. These results indicate that BNST and CeA, and dynorphin neurons specifically, are engaged during drinking behavior, and activity dynamics are influenced by stimulus novelty and chronic alcohol. • BNST and CeA calcium activity increases during drinking of alcohol and other fluids. • BNST and CeA dynorphin neurons are engaged during alcohol consumption. • BNST and CeA activity is higher when taste stimuli are novel. • BNST and CeA calcium activity during drinking is reduced after chronic alcohol. • BNST-CeA coherence is increased during alcohol drinking bouts in male mice. [ABSTRACT FROM AUTHOR]

Ethanol-Paired Conditioned Stimuli (CS) can increase ethanol-responding either in extinction or occurring at low rates late in a session. To examine the generality of CS-induced increases in ethanol-responding, we examined whether a CS could increase responding suppressed by Conditioned-Taste-Aversion (CTA), which presumably suppresses responding by changing ethanol's valence from positive to negative. Rats were trained to respond for ethanol under a Random Interval (RI) schedule. We then removed the lever and paired Random-Time ethanol deliveries with illumination of a stimulus light (i.e., CS) for 10 sessions. Results were compared with a Truly Random Control group, in which the light and ethanol deliveries occurred independently. In a subsequent experiment, rats were treated similarly, except the light served as a discriminative stimulus, as the lever was extended and ethanol deliveries were available under a RI during light presentations. After this training, the lever was returned and rats again responded for ethanol. Subsequently, sessions were followed by LiCl administration. When responding reached low levels, LiCl administration stopped and the light was occasionally illuminated during the session. Responding during the light presentation was compared to responding during the period preceding light presentation. Responding partially recovered across 10 sessions and was greater during light presentations than in the period before it in all three groups. Increases were not reliably different between the groups, indicating that explanations for these increases such as CS-induced increases in motivation or approach toward the light are unlikely to be correct. The most likely explanation for these light-induced increases is that during sessions in which the light had been presented previously, LiCl had never been presented and thus, the light had come to signal that ethanol was safe to drink. • An ethanol-paired CS increased ethanol-responding that had been suppressed by a conditioned-taste-aversion. • Such increases could support the notion that ethanol-paired conditioned stimuli increase ethanol-seeking by increasing motivation to drink. • These increases are not easily explained by dishabituation, nor by the CS acting as a US representation. • The most consistent explanation is that the CS serves as a signal when ethanol ingestion is safe. [ABSTRACT FROM AUTHOR]

Chronic alcohol consumption can lead to tolerance and escalation of drinking in humans and animals, but mechanisms underlying these changes are not fully characterized. Preclinical models can delineate which mechanisms are involved. The chronic intermittent ethanol exposure (CIE) procedure uses forced exposure to vaporized alcohol that elicits withdrawal and increased responding for alcohol in operant tasks in C57BL/6J inbred mice. Chronic two-bottle choice (2BC) drinking in the same strain elicits abstinent-related depression-like behavior, suggestive of allostatic changes. Selected lines such as crossed High Alcohol Preferring (cHAP) mice voluntarily drink to blood alcohol concentrations comparable to those attained in CIE and could be used to assess how alcohol affects these same endpoints without the confounds of involuntary vapor inhalation. In three experiments, we assess how 2BC drinking in cHAP mice affects abstinence-related depressive- and anxiety-like behavior, operant responding for alcohol, and binge consumption using drinking-in-the-dark (DID). We hypothesized that cHAPs with home-cage drinking experience would exhibit more depressive behavior after abstinence, increased responding for alcohol in the operant box, and increased DID intake. Of these, a drinking history increased DID intake in female cHAPs only and increased sucrose preference and intake following abstinence, but had no effects on operant responding or NSFT latency and FST immobility following forced abstinence. These results are consistent with recent findings using slice electrophysiology showing tolerance to alcohol's actions on the dorsolateral striatum following 2BC drinking in female, but not male cHAP mice. Overall, these data suggest that cHAPs may require procedures allowing rapid intoxication, such as DID, to demonstrate changes in alcohol's rewarding effects. • Up to 3 weeks of abstinence from 2BC drinking did not induce affective disturbance. • Alcohol drinking experience did not change operant responding for alcohol. • Alcohol drinking experience did not change extinction responding for alcohol. • Alcohol experience increased intake in drinking-in-the-dark in female cHAPs only. • During DID, alcohol experience caused more persistent binge-like behavior. [ABSTRACT FROM AUTHOR]

Problematic alcohol use is a serious threat to the behavioral health of active-duty Service Members (ADSM), resulting in numerous calls from governmental agencies to better understand mechanistic factors contributing to alcohol misuse within the military. Alcohol use motives are reliable predictors of alcohol-related behaviors and are considered malleable targets for prevention and intervention efforts. However, empirical research indicates that drinking motives vary across contextually distinct populations. Although some research has been conducted among veteran and reservist populations, limited work has been specifically focused on ADSM and no research has evaluated motives and alcohol metrics among ADSM based on military rank. Participants for the current study included 682 ADSM recruited from a large military installation in the U.S. Structural equation modeling evaluated associations between four drinking motives (i.e., enhancement, social, conformity, coping) and three alcohol misuse metrics (i.e., alcohol frequency, binge frequency, alcohol problems). Three models were evaluated: one full (combined) model and two separate models based on military rank – junior enlisted (i.e., E1–E4) and non-commissioned officers (NCOs) (i.e., E5–E9). Results for junior enlisted ADSM indicated that coping and enhancement motives were most strongly associated with all alcohol misuse metrics. However, among NCOs, results indicated that alcohol problems were only associated with coping motives. Notably, results also indicated that alcohol use motives accounted for substantively more variance across all alcohol-related metrics among NCOs. Findings generally support extant military-related literature indicating use of alcohol for coping (e.g., with anxiety) as the motivation most consistently associated with increased alcohol misuse. However, novel findings highlight enhancement motives – using alcohol to attain some positive internal reward – as another, often stronger, motivation impacting alcohol use outcomes. Further, findings highlight notable distinctions between alcohol use motives (i.e., coping vs. enhancement) and the impact of alcohol use motives (i.e., effect size) on alcohol metrics between junior enlisted and NCOs. • Generally, coping and enhancement motives were most strongly linked to alcohol misuse. • Enhancement motives impacted junior enlisted alcohol use more than coping motives. • Only coping motives were associated with alcohol problems among NCOs. • Alcohol outcomes of NCOs were more impacted by motives than junior enlisted ADSM. [ABSTRACT FROM AUTHOR]

Recent studies revealed that any amount of alcohol consumption is an overall health detriment to multiple populations, contrary to popular beliefs. In addition, very few alcohol use studies utilized machine learning methods to compare the biological health of moderate drinkers compared to those that abstain from alcohol consumption, opting instead to focus on binge drinking and heavy drinking. Using participant data of multiple factor types from the National Health and Nutrition Examination Survey, we created prediction models with stacked ensembles and gradient boosting models. Machine learning models were used to identify which factors most enabled the prediction of moderate drinking behaviors. Our combined factor runs produced a cross-validation area under the curve (AUC) of 0.929 and a validation area under the curve of 0.806. Runs that only included biochemical or demographical factors received cross-validation AUC values of 0.825 and 0.925, and validation AUC values of 0.757 and 0.783, respectively. The top predictive factors for our machine learning runs, including gamma glutamyl transferase, gender, iron levels, and cigarette and marijuana usage, corroborate past studies that link those factors to alcohol consumption. Our findings identified key differences in the biological health of moderate drinkers compared to those that abstain from drinking. These results reveal a need to further explore the health effects of moderate drinking, especially for vulnerable populations. • Recent studies concluded that any alcohol consumption is unhealthy for many groups. • These results refute previous research stating that healthy drinking levels exist. • There are biochemical differences found between abstinent and moderate drinkers. • Moderate drinking may have more effects upon bodily health than previously thought. [ABSTRACT FROM AUTHOR]

Chronic alcohol use induces innate immune genes, which activate the innate immune system. Neuroimmune regulatory proteins [e.g., Cluster of Differentiation 200 (CD200)] are immune response regulators and are involved in balancing the immune response. This study aimed to investigate the expression of CD200 on the surface of peripheral blood leukocytes in patients with alcohol use disorder and compare them with controls. Fifty male patients with alcohol use disorder were included in the study. A baseline assessment was done, and alcohol use history, craving, and withdrawal scores were collected. A 2-mL venous blood sample was collected from cases and controls for immunophenotyping of CD200. The control group consisted of 50 participants with similar socio-economic backgrounds. The cellular expression of CD200 on total leukocytes (median ± IQR) [39.94 (28.85, 50.01)] in cases was significantly lower compared to controls [45.07 (37.70, 51.69)] (U = 896, p = 0.015). Expression of CD200 on lymphocytes in cases was negatively correlated with years of heavy drinking and this was statistically significant (r = −0.321, p = 0.023). The study indicates that cellular expression of CD200 on the surface of peripheral blood leukocytes is reduced in alcohol-dependent patients. This reduction can contribute to exaggerated immune activity, release of pro-inflammatory cytokines, chronic microglial activation, neuroinflammation, and neurodegeneration in alcohol dependence. • Chronic alcohol consumption leads to activation of the neuroimmune system. • Cluster of differentiation (CD200) is a neuroimmune-regulating protein. • Cellular expression of CD200 on leukocytes is reduced in alcohol-dependent individuals. • Reduced CD200 can contribute to an exaggerated immune response in alcohol dependence. [ABSTRACT FROM AUTHOR]

Methyl alcohol intoxication causes severe morbidity and mortality, especially in developing countries. Formic acid is formed as a result of methanol metabolism. Formic acid accumulation and inhibition of adenosine triphosphate synthesis result in ophthalmic issues. This study aimed to demonstrate that the optic nerve sheath diameter (ONSD) measurement is an accurate prognostic marker and can be helpful in the diagnosis of methanol intoxication. This prospective study was conducted with 52 patients who were admitted to the emergency department after alcohol consumption and agreed to participate in the study. Age, gender, comorbid diseases, vital signs, ONSD ultrasonography measurements, hospitalization and discharge status, in-hospital mortality status, dialysis need, presence of visual impairment, blood gas parameters, respiratory status, time since alcohol intake, ethanol levels, urea levels, and creatinine levels were analyzed. ROC curve analysis was performed to evaluate the predictive power of ONSD to diagnose methanol intoxication. The area under the curve was 0.857 for the cut-off value of 5.05 mm (95 % CI: 0.728–0.985; p < 0.001), with a sensitivity of 80.8 % and a specificity of 100 %. In the regression analysis performed to determine the prognostic value of the parameters in estimating mortality in methanol intoxication cases, an increase in ONSD (OR: 3.619; 95 % CI: 0.057–0.199; p = 0.001), an increase in lactate levels (OR: 5.653; 95 % CI: 0.040–0.085; p < 0.001), and increased duration after alcohol intake (OR: 2558; 95 % CI: 0.004–0.034; p = 0.014) were identified as independent predictors of mortality, but pH, HCO 3 , and base deficit levels were not significant predictors. We believe that ONSD can be helpful for the differential diagnosis and prognosis of patients with suspected methanol toxicity who presented with alcohol intake. • As a result of our study, it was observed that ONSD increased in cases of methanol intoxication, but there was no increase in ONSD in patients who took ethyl alcohol. • ONSD can be used in the differential diagnosis of cases with suspected methanol intoxication due to alcohol intake. • We think that ONSD can be used to predict the prognosis of cases with suspected methanol intoxication and admitted due to alcohol consumption. [ABSTRACT FROM AUTHOR]

The aim of the present study was to determine the effects of binge drinking on anxiety-like, depression-like, and social behavior. The participation of the corticotropin-releasing factor (CRF) receptors (CRF1 and CRF2) in these effects was also investigated. Therefore, male C57BL/6 mice were exposed to drinking in the dark, a classical animal model for binge drinking, and treated intracerebroventricularly (icv) with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin 2 B, immediately or 24 h after binge drinking. After 30 min, the animals were investigated in an elevated plus-maze test and a forced swim test for anxiety-like and depression-like signs, respectively. In addition, mice were tested in a three-chamber social interaction arena for sociability and preference for social novelty. Immediately after binge drinking, mice exposed to alcohol expressed anxiolytic and antidepressant effects, which were reduced by astressin 2 B, but not antalarmin. Moreover, mice exposed to alcohol showed increased sociability and preference for social novelty immediately after binge drinking. In contrast, 24 h after binge drinking mice exposed to alcohol presented anxiety-like and depression-like signs, which were reversed by antalarmin, but not astressin 2 B. However, mice exposed to alcohol did not show any significant change in social interaction after 24 h. The present study demonstrates that alcohol exerts different effects on anxiety-like, depression-like, and social behavior immediately and a day after binge drinking, and that the anxiolytic and antidepressant effects produced by binge drinking are mediated by CRF2, whereas the anxiety-like and depression-like signs observed the next day are promoted by CRF1. • Mice exposed to alcohol expressed anxiolytic and antidepressant effects. • Mice exposed to alcohol also showed enhanced sociability and preference for social novelty. • Mice exposed to alcohol withdrawal presented anxiety-like and depression-like signs. • Mice exposed to alcohol did not show any change in social interaction. • Alcohol has different effects on behavior immediately and a day after binge drinking. [ABSTRACT FROM AUTHOR]

Alcohol overconsumption is well known to cause damage to the peripheral nervous system. The aim of this study was the functional and structural evaluation of the small nerve fibers in alcohol-dependent subjects, with or without symptoms of peripheral neuropathy. Twenty-six consecutive alcohol-dependent subjects treated for detoxification voluntarily in the specialized unit of the Athens University Psychiatric Clinic were enrolled in this prospective study over 18 months. Every subject was assessed by peripheral nerve evaluation using the Neuropathy Symptoms Score (NSS) and Neuropathy Impairment Score (NIS), followed by nerve conduction studies (NCS), quantitative sensory testing (QST), and skin biopsy. Twenty-nine normal subjects, age- and gender-matched, constituted the control group. Peripheral neuropathy was diagnosed in 16 subjects (61.5%). Among these 16 subjects, pure large fiber neuropathy (LFN) was found in two subjects (12.5%), pure small fiber neuropathy (SFN) was found in eight subjects (50%), and both large and small fiber neuropathy was diagnosed in six patients (37.5%). The intraepidermal nerve fiber density (IENFD) of the patients' skin biopsy was significantly lower than that of the control group. Additionally, QST results showed a statistically significant sensory impairment in the patients. Our study confirms small fiber neuropathy due to alcohol abuse with a high prevalence of pure SFN that might have remained undetected without QST and IENFD. • Skin biopsy and quantitative sensory testing were used to detect pure small fiber neuropathy in alcohol dependency. • Skin biopsy correlation with nerve conduction studies, quantitative sensory testing and clinical parameters. • High incidence of pure small fiber neuropathy that might have remained undetected without using QST and skin biopsies. [ABSTRACT FROM AUTHOR]

There are no studies that have utilized both biomarkers and self-reported data to evaluate maternal alcohol use during pregnancy in Mexico. Therefore, we aimed to describe the prevalence of alcohol consumption in a cohort of 300 Mexican pregnant women. We used a validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to measure hair ethyl glucuronide (EtG) in hair segments that corresponded to the first and second half of pregnancy. We compared the hair EtG values to a self-reported questionnaire on maternal drinking habits and evaluated whether the gestational alcohol use was associated with psychotropic drug use. Based on the EtG measurements, 263 women (87.7%) were alcohol-abstinent during the entire pregnancy, while 37 (12.3%) had used alcohol at least once during the pregnancy. Of these, only two women were found to have problematic alcoholic behavior during the entire pregnancy. No significant differences in sociodemographic characteristics were observed between alcohol-abstinent women and women with drinking habits. The self-reporting data and hair EtG gave heterogeneous results: although 37 women had self-reported alcohol use during pregnancy, only 54.1% of these women tested positive for hair EtG. Of the women who tested positive for hair EtG, 54.1% tested positive for psychoactive substances. In our cohort, the use of drugs of abuse was independent of gestational drinking. This study provided the first objective evidence of prenatal ethanol consumption in a cohort of Mexican pregnant women. • Gestational alcohol use is best evaluated using both biomarkers and self-reported data. • Maternal hair ethyl glucuronide can be used as a biomarker for alcohol use. • The objective measures can be used to screen children at risk of FASD. • Providing clear information to pregnant women can help them quit drinking. [ABSTRACT FROM AUTHOR]

The influence of Pavlovian Conditioned Stimuli (CS) on ethanol self-administration and choice between ethanol and an alternative are potentially important. Ethanol-paired CS might increase ethanol self-administration, especially when it has been reduced during recovery, though the selectivity of these increases has been questioned. To date, one study examined the effects of an ethanol-paired CS on ethanol choice and found that the CS increased ethanol-responding more than food-responding when both were in extinction. However, it remains unclear whether ethanol-paired CS increase ethanol-choice that is not in extinction. Here, we examine the effects of an ethanol-paired CS on ethanol-choice when both food- and ethanol-responding are reinforced. Sixteen adult male Lewis rats were trained on a concurrent schedule to respond for ethanol on one lever and for food on the other lever. Ethanol was available under an FR 5 schedule, and food was available under an FR schedule that was adjusted for each rat to earn an equal number of food and ethanol deliveries. Then, 2-min light presentations were paired with an RT 25-sec schedule of ethanol delivery for 10 sessions in the absence of both levers. After this, subjects were placed back on the concurrent schedule for one session, then five sessions with the CS being present or absent on each trial of the concurrent schedule occurred. Rats learned to respond on one lever for ethanol and on the other for food and earned similar numbers of ethanol and food deliveries. During Pavlovian Conditioning, the number of head entries into the head-entry detector was higher in the presence of the CS than in its absence. In the test sessions, rats made more ethanol responses in the presence of the CS than in its absence. However, this effect was small and did not increase the amount of ethanol earned. Thus, ethanol-paired CS could increase ethanol-responding under a choice procedure but did not increase ethanol consumption meaningfully under the studied conditions. • Ethanol-paired conditioned stimulus increased ethanol-responding when both ethanol and an alternative were reinforced. • A Pavlovian conditioned stimulus effect on drinking was not robust, and it did not increase the amount of ethanol earned. • The effects of conditioned stimulus on ethanol choice when ethanol and food stimuli were not in extinction are shown. [ABSTRACT FROM AUTHOR]

We assessed the feasibility and acceptability of using BACtrack Skyn wearable alcohol monitors for alcohol research in a college student population. We enrolled n = 5 (Sample 1) and n = 84 (Sample 2) Indiana University undergraduate students to wear BACtrack Skyn devices continuously over a 5-day to 7-day study period. We assessed feasibility in both samples by calculating compliance with study procedures, and by analyzing amount and distributions of device output [e.g., transdermal alcohol content (TAC), temperature, motion]. In Sample 1, we assessed feasibility and acceptability with the Feasibility of Intervention Measure (FIM) scale and the Acceptability of Intervention Measure (AIM) scale. All participants were able to successfully use the alcohol monitors, producing a total of 11,504 h of TAC data. TAC data were produced on 567 days of the 602 total possible days of data collection. The distribution of the TAC data showed between-person variation, as would be expected with between-person differences in drinking patterns. Temperature and motion data were also produced as expected. Sample 1 participants (n = 5) reported high feasibility and acceptability of the wearable alcohol monitors in survey responses with a mean FIM score of 4.3 (of 5.0 possible score) and mean AIM score of 4.3 (of 5.0 possible score). The high feasibility and acceptability we observed underscore the promise of using BACtrack Skyn wearable alcohol monitors to improve our understanding of alcohol consumption among college students, a population at particularly high risk for alcohol-related harms. • BACtrack Skyn wearable alcohol devices were feasible and acceptable for use among college students. • Data were collected over 5–7 days in naturalistic drinking environments. • High feasibility and acceptability were observed in survey responses and operational measures. [ABSTRACT FROM AUTHOR]

Recent developments in wearable technologies have allowed for device-based capture of alcohol concentration among participants in their natural environments. Currently, the Continuous Alcohol Monitor from SCRAM systems (SCRAM-CAM) is the most extensively studied and validated transdermal alcohol concentration (TAC) sensor. However, there has been relatively little work focusing on its acceptability from the participants' perspective. In the current study, we assess the user experience of the SCRAM-CAM anklet in a sample of 222 regularly heavy drinking young adults (mean age = 22.3) who wore the anklet in their natural environments for five 24-h periods spanning 6 consecutive days. Differences in the anklet user experience were measured along a number of dimensions, and differences were tested by sex at birth, white/non-white racial/ethnic group membership, and alcohol use disorder (AUD) risk (measured through Alcohol Use Disorder Identification Test [AUDIT] scores). Males and females differed significantly on six of the eight acceptability items, with males showing more positive responses toward the anklet than females. No differences were found by white/non-white racial/ethnic groups nor AUD risk. Results suggest positive levels of acceptability toward the device overall while in natural environments, further validating the usage of the device in studies that measure alcohol consumption among different groups, including those with high levels of alcohol consumption. Researchers should take into consideration the different levels of burden or discomfort in male versus female participants when using the device. • Results showed positive levels of acceptability toward the SCRAM-CAM and low levels of anklet influence while drinking. • Sex differences were found in six of eight acceptability items when reporting their anklet user experience. • Males reported scores that were associated with a more positive experience with the SCRAM-CAM anklet device. • No differences in anklet user experience were found in white/non-white racial/ethnic group or by their AUDIT score. [ABSTRACT FROM AUTHOR]

On October 26th, 2022 the annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held as a satellite symposium at the annual meeting of the Society for Leukocyte Biology in Hawaii. The 2022 meeting focused broadly on the immunological consequences of acute, chronic, and prenatal alcohol exposure and how these contribute to damage in multiple organs and tissues. These included alcohol-induced neuroinflammation, impaired lung immunity, intestinal dysfunction, and decreased anti-microbial and anti-viral responses. In addition, research presented covered multiple pathways behind alcohol-induced cellular dysfunction, including mitochondrial metabolism, cellular bioenergetics, gene regulation, and epigenetics. Finally, the work presented highlighted potential biomarkers and novel avenues of treatment for alcohol-induced organ damage. • Alcohol disrupts immune cell bioenergetics and metabolism. • Ethanol changes epigenetic processes that alter neurogenesis in the brain. • Ethanol stimulates changes in the gut that contribute to neuroinflammation after injury. • Ethanol-induced intestinal dysfunction is reversed by rIL-27 or short chain fatty acids. • The age at which alcohol exposure occurs influences the inflammatory response. [ABSTRACT FROM AUTHOR]

New-generation transdermal monitors such as the ION Research Alpha Prototypes (ION RAP) hold promise for real-time alcohol measurement, with improvements in design features such as sampling frequency, size, and comfort. This paper aims to provide the first comparisons of the wrist-worn enzyme-based ION RAP and the fuel cell-based SCRAM-CAM against breath alcohol concentration (BrAC) readings. Participants (N = 23) completed a total of 69 laboratory alcohol administration sessions while wearing both a prototype of the ION RAP wristband and a SCRAM-CAM ankle monitor; they also gave breath samples each 10 min. Analyses focused on latencies of transdermal alcohol concentration (TAC) after alcohol ingestion, correlations, and cross-correlations between BrAC and TAC measurements. A high failure rate of the ION RAP was observed (61.5% of the sessions were excluded due to the sessions not containing enough valid data). On average, the SCRAM-CAM and ION RAP detected alcohol 43 (SD = 21) and 50 (SD = 27) minutes after the first drink, with peak values reached after 138 (SD = 47) and 154 (SD = 56) minutes, respectively. SCRAM-CAM TAC peak (r = 0.185, p = 0.375) and area under the curve (AUC; r = 0.320, p = 0.118) showed small- and medium-sized correlations to BrAC. ION RAP TAC peak (r = −0.082, p = 0.698) and AUC (r = 0.040, p = 0.852) correlations to BrAC were close to zero. In this study, the new-generation ION RAP and the traditionally used SCRAM-CAM show similar delays in detection and similar TAC curves over time, despite using either enzyme- or fuel cell-based technologies, respectively. Due to high failure rates of the ION RAP prototypes and close to zero correlations to BrAC, further developments and improvements of these TAC wristbands are required for reliable and valid use in real-time alcohol measurement. • The transdermal alcohol monitors ION RAP and SCRAM-CAM were evaluated against breath alcohol concentration. • The failure rate for the ION RAP wristband was 62% and 0% for the SCRAM-CAM. • The enzyme-based ION RAP and fuel-cell SCRAM-CAM had similar alcohol detection delays. • BrAC correlations were higher for SCRAM-CAM (r = 0.19–0.32) than for ION RAP (r = −0.09–0.04). • Maximal cross-correlation coefficients ranged from 0.63 to 0.67. [ABSTRACT FROM AUTHOR]

College drinkers commonly report blacking out (i.e., alcohol-induced amnesia), and those who drink with the intention to blackout are at risk for harmful consequences. Drunkorexia (i.e., restriction of calories on planned drinking days) is a high-risk behavior potentially associated with blacking out. Informed by the Theory of Planned Behavior (TPB), this study explores blackout experiences and intentions to blackout association with drunkorexia. College students (n = 2335) who primarily identified as female and White participated via an online survey. Participants received a $3 coupon for completion of the study. Consistent with the literature, 40% and 60.7% of participants reported experiencing blackouts and drunkorexia, respectively, in the last year. Informed by the TPB, a structural equation model assessed whether more frequent blackout experiences (IV) were related to drunkorexia behaviors (DV1) and alcohol behaviors (DV2), and whether there was a significant indirect effect through blackout intention. The model fit the data well (CFI =.98, TLI =.95), which suggests that more frequent blackout experiences relate to more drunkorexia experiences (R2 =.04) and higher levels of alcohol consumption (R2 =.44). In addition, the relationship between blackout experiences and drunkorexia flows through intentions to blackout (i.e., a significant indirect effect). Findings are consistent with TPB, which suggests that intentions predict health behavior. Future interventions should consider modifying intentions and other possible TPB constructs to minimize high-risk alcohol consumption and drunkorexia behaviors. • College students who intend to blackout are likely to engage in alcohol consumption, suggesting that intentions to experience blackouts are high among college students who frequently engage in heavy drinking and experience alcohol-related consequences. • Lifetime history of blackouts relates to current drunkorexia behaviors, and frequency of recent drinking relates to future intention to blackout. • This study confirms that intentions predict negative health behavior, including drunkorexia, a riskier alcohol consumption behavior, among college students. [ABSTRACT FROM AUTHOR]

Exposure to substances of abuse during pregnancy can have long-lasting effects on offspring. Alcohol is one of the most widely used substances of abuse that leads to the most severe consequences. Recent studies in the United States, Canada, and the United Kingdom showed that between 1% and 7% of all children exhibit signs and symptoms of fetal alcohol spectrum disorder (FASD). Despite preventive campaigns, the rate of children with FASD has not decreased during recent decades. Alcohol consumption often accompanies exposure to such drugs as tobacco, cocaine, opioids, and cannabis. These interactions can be synergistic and exacerbate the deleterious consequences of developmental alcohol exposure. The present review focuses on interactions between alcohol and cannabis exposure and the potential consequences of these interactions. • Cannabis is the most frequently used illicit drug among pregnant women. • Half of pregnant women who report cannabis use, also report the consumption of alcoholic beverages. • Early alcohol and cannabis exposure is linked to worse developmental outcomes than exposure to either drug alone. • Alcohol and cannabinoids exert a synergistic effect during early development through the endocannabinoid system. [ABSTRACT FROM AUTHOR]

Prenatal alcohol exposure can impair placentation and cause intrauterine growth restriction (IUGR), fetal demise, and fetal alcohol spectrum disorder (FASD). Previous studies showed that ethanol's inhibition of placental insulin and insulin-like growth factor, type 1 (IGF-1) signaling compromises trophoblastic cell motility and maternal vascular transformation at the implantation site. Since soy isolate supports insulin responsiveness, we hypothesized that dietary soy could be used to normalize placentation and fetal growth in an experimental model of FASD. Pregnant Long-Evans rat dams were fed with isocaloric liquid diets containing 0% or 8.2% ethanol (v/v) from gestation day (GD) 6. Dietary protein sources were either 100% soy isolate or 100% casein (standard). Gestational sacs were harvested on GD19 to evaluate fetal resorption, fetal growth parameters, and placental morphology. Placental insulin/IGF-1 signaling through Akt pathways was assessed using commercial bead-based multiplex enzyme-linked immunosorbent assays. Dietary soy markedly reduced or prevented the ethanol-associated fetal loss, IUGR, FASD dysmorphic features, and impairments in placentation/maturation. Furthermore, ethanol's inhibitory effects on the placental glycogen cell population at the junctional zone, invasive trophoblast populations at the implantation site, maternal vascular transformation, and signaling through the insulin and IGF1 receptors, Akt and PRAS40 were largely abrogated by co-administration of soy. Dietary soy may provide an economically feasible and accessible means of reducing adverse pregnancy outcomes linked to gestational ethanol exposure. • Gestational dietary soy consumption prevents fetal loss, intrauterine growth restriction, and critical dysmorphic craniofacial features of fetal alcohol spectrum disorder. • Dietary soy isolate preserves the integrity of placentation despite continuous high-level gestational alcohol exposure. • Soy isolate preserves the integrity of placental insulin signal transduction through Akt cell survival and metabolic pathways in an experimental fetal alcohol spectrum disorder model. • Soy isolate enhances development in control animals, suggesting it may provide an accessible means to globally reduce rates of low birth weight. [ABSTRACT FROM AUTHOR]

Hemorrhage is a major component of traumatic brain injury (TBI). Red blood cells, accumulated at the hemorrhagic site, undergo hemolysis upon energy depletion and release free iron into the central nervous system. This iron must be managed to prevent iron neurotoxicity and ferroptosis. As prior alcohol consumption is often associated with TBI, we examined iron regulation in a rat model of chronic alcohol feeding subjected to fluid percussion-induced TBI. We found that alcohol consumption prior to TBI altered the expression profiles of the lipocalin 2/heme oxygenase 1/ferritin iron management system. Notably, unlike TBI alone, TBI following chronic alcohol consumption sustained the expression of all three regulatory proteins for 1, 3, and 7 days post-injury. In addition, alcohol significantly affected TBI-induced expression of ferritin light chain at 3 days post-injury. We also found that alcohol exacerbated TBI-induced activation of microglia at 7 days post-injury. Finally, we propose that microglia may also play a role in iron management through red blood cell clearance. • Alcohol consumption prior to TBI sustained expression of LCN2, HO-1, and F-LC. • Alcohol directly affected TBI-induced F-LC expression at 3 days post-injury. • Alcohol also affected TBI-induced activation of microglia at 7 days post-injury. [ABSTRACT FROM AUTHOR]

Only a small minority of all attempts to stop smoking are successful, especially among smokers who are heavy drinkers and those with an alcohol use disorder. The current systematic review focuses on the negative effects of alcohol use, either before or during attempts to quit smoking, on the success rate of these attempt(s) in alcohol-drinking tobacco smokers. We conducted a systematic review of naturalistic and experimental studies, which included at least 40 tobacco smokers with a recorded drinking status (non-drinking, heavy drinking, alcohol use disorder) and a clearly documented change in alcohol consumption. We could not conduct a meta-analysis and, thus, used consistency across studies to draw conclusions. The evidence presented here shows that alcohol use is associated with lower rates of success in quitting smoking in 20 out of 27 studies. This includes both lapses and relapses. Similarly, in 19 out of 20 long-term follow-up studies, the duration of smoking abstinence was shorter among persons with higher alcohol consumption. Finally, 12 out of 13 experimental studies showed that exposure of smokers to alcohol cues or to drinking of alcohol induce a strong propensity to smoke. It is, therefore, recommended for smokers who drink alcohol and who intend to quit smoking to use an integrated approach, i.e., to stop or substantially reduce their alcohol consumption before and/or during their attempt to quit smoking. • The co-occurrence of tobacco smoking and alcohol consumption has been well documented. • Smoking cessation has a rather low success rate. • Being a non-drinker compared to a drinker is associated with a more successful smoking cessation outcome. • Low alcohol consumption compared to heavy drinking or an alcohol use disorder is associated with a more successful smoking cessation outcome. • Smokers should be strongly advised to stop or largely reduce alcohol consumption during a smoking cessation attempt. [ABSTRACT FROM AUTHOR]

Wrist-worn transdermal alcohol concentration (TAC) sensors have the potential to provide detailed information about day-level features of alcohol use but have rarely been used in field-based research or in early adulthood (i.e., 26–40 years) alcohol users. This pilot study assessed the acceptability, user burden, and validity of using the BACtrack Skyn across 28 days in individuals' natural settings. Adults aged 26–37 (N = 11, M age = 31.2, 55% female, 73% non-Hispanic white) participated in a study including retrospective surveys, a 28-day field protocol wearing Skyn and SCRAM sensors and completing ecological momentary assessments (EMA) of alcohol use and duration (daily morning reports and participant-initiated start/stop drinking EMAs), and follow-up interviews. Day-level features of alcohol use extracted from self-reports and/or sensors included drinks consumed, estimated Blood Alcohol Concentration (eBAC), drinking duration, peak TAC, area under the curve (AUC), rise rate, and fall rate. Repeated-measures correlations (r rm) tested within-person associations between day-level features of alcohol use from the Skyn versus self-report or the SCRAM. Participants preferred wearing the Skyn over the SCRAM [ t (10) = −6.79, p <.001, d = 2.74]. Skyn data were available for 5614 (74.2%) out of 7566 h, with 20.7% of data lost due to syncing/charging issues and 5.1% lost due to device removal. Skyn agreement for detecting drinking days was 55.5% and 70.3% when compared to self-report and the SCRAM, respectively. Correlations for drinking intensity between self-report and the Skyn were 0.35 for peak TAC, 0.52 for AUC, and 0.30 for eBAC, which were smaller than correlations between self-report and SCRAM, at 0.78 for peak TAC, 0.79 for AUC, and 0.61 for eBAC. Correlations for drinking duration were larger when comparing self-report to the Skyn (r rm = 0.36) versus comparing self-report to the SCRAM (r rm = 0.31). The Skyn showed moderate-to-large, significant correlations with the SCRAM for peak TAC (r rm = 0.54), AUC (r rm = 0.80), and drinking duration (r rm = 0.63). Our findings support the acceptability and validity of using the Skyn for assessing alcohol use across an extended time frame (i.e., 28 days) in individuals' natural settings, and for providing useful information about day-level features of alcohol use. • Individuals reported high acceptability for using the Skyn across 28 days. • Participants preferred using the Skyn versus the SCRAM in natural settings. • The Skyn showed similar probability to the SCRAM for detecting drinking days. • Skyn day-level alcohol use features correlated with self-report and the SCRAM. • The Skyn provided useful information about day-level features of alcohol use. [ABSTRACT FROM AUTHOR]

Background: This study investigated the influence of social incentives, alcohol incentives, and responsibility disincentives on decisions to attend and drink at party events in young adult college students (n = 82; 55 women, 27 men) where 36 (20 women; 16 men) had an Alcohol Use Disorder (AUD) and 46 (35 women; 11 men) were Control participants without an AUD.Methods: In this within-subjects design participants were presented with a series of hypothetical drinking event scenarios that varied in terms of social incentives (knowing many versus few people), alcohol incentives (more versus less alcohol available), and next day responsibility disincentives (high vs moderate vs low). Participants were asked whether they would attend the event and how many drinks they would consume.Results: Social incentives significantly predicted both decisions to attend party events and decisions about how much to drink for all participants. Participants were more likely to decide to attend and drink more at high social incentive party events (where they knew more people). However, while low social incentives generally discouraged attendance decisions, AUD participants were more likely than controls to decide to attend party events in low social incentive contexts. Alcohol incentives did not affect attendance decisions. However, alcohol incentives did increase drinking amount decisions for AUD participants. Finally, while disincentives decreased attendance and drinking amount decisions in general, AUD participants were less deterred by responsibility disincentives than Controls.Conclusions: The results highlight the important influence of social rewards on drinking related decisions and suggest individual differences in how incentives and disincentives affect drinking decisions in persons with an AUD. [ABSTRACT FROM AUTHOR]

There are substantial inter-individual variations in alcohol metabolism and response that are likely due to sex and age; however, these are not well understood. We investigated age and sex influences on alcohol elimination rate (AER) and subjective responses following intravenous (IV) administration in non-dependent drinkers. Participants underwent a 2-session study where they received IV alcohol (target breath alcohol level: 0.05 g%) and placebo in counter-balanced order. AER was higher in males than in females across age groups. These differences were partly explained by sex differences in lean body mass and liver volume. Alcohol significantly increased peak feelings of high, intoxication, drug-effects, liking-effects, and wanting-more, with no major sex differences. There were no age-related differences in feelings of high and intoxication; however, the older group reported significantly lower peak liking-effects and stimulation responses than the younger group. These findings highlight the significant impact of sex and age as sources of variability in the clinical pharmacology of alcohol. • Alcohol elimination rates and subjective responses were assessed in younger (21–25 years) and older (55–65 years) men and women. • Alcohol elimination rates were higher in men than in women; and explained by sex differences in lean body mass and liver volume. • Subjective perceptions of high, intoxication, drug liking, and wanting more alcohol did not differ by sex. • The older group reported similar feelings of high and intoxication but lower liking and stimulation than the younger group. • These findings highlight the impact of sex and age as sources of variability in the clinical pharmacology of alcohol. [ABSTRACT FROM AUTHOR]

Alcohol use is increasing among adults 65 and older and the size of this population is expanding rapidly. Aging is associated with systemic inflammation, sleep disturbances, cancers, cognitive decline, and increased risk of injury and death from falls and other accidents. Alcohol misuse exacerbates and accelerates these age-related changes. Older drinkers are more sensitive to acute alcohol-induced impairments in memory, coordination, reaction time, and driving performance. Oxidative stress and DNA damage resulting from chronic heavy alcohol consumption contribute to an increased risk of cancer, liver disease, and cardiovascular disease. Medication use increases with age and many medications prescribed to older adults can interact negatively with alcohol. The rapid expansion of the population aged 65 and older, combined with higher levels of alcohol use and AUD in the Baby Boomer cohort than the preceding generation, could significantly increase the burden of alcohol on the healthcare system resulting from AUD and alcohol-related injuries and diseases. Screening and brief intervention for hazardous alcohol use among older patients along with education regarding potential interactions between alcohol and medications could substantially reduce the risk of harms from alcohol but currently is underutilized. • The population aged 65+ is growing and so are levels of alcohol consumption and AUD in this age group. • Changes in physiology during aging lead to higher BAC levels and bigger impairments in behavior and cognition. • Physicians should talk with older patients about the risks of alcohol. [ABSTRACT FROM AUTHOR]

While the detrimental effects of binge drinking are well recognized, low-to-moderate alcohol consumption may be beneficial to health, although the underlying mechanism(s) remains elusive. In this opinion article, we will examine the effects of low dose alcohol consumption from the perspective of epigenetic modulation. Biochemically, alcohol is metabolized into acetate and subsequently to acetyl-coA, which can modulate histone acetylation levels. While elevated levels of acetyl-CoA are detrimental for longevity, we argue that diminished acetyl-CoA also negatively affects fatty acid biosynthesis and histone acetylation, which play a critical role in gene expression and, ultimately, health span. Since mitochondrial function and glucose metabolism, which provide the main source of nucleocytoplasmic acetyl-CoA, are compromised with age, alcohol-derived acetate could be an alternative source of acetyl-CoA to compensate. Hence, the health benefits of low ethanol consumption may be more pronounced after midlife, since mitochondrial function and/or glucose metabolism are diminished in this phase of the life course. Indeed, various clinical alcohol consumption studies concur with this notion, and have shown that a low dose of regular alcohol intake after midlife brings about various health and survival benefits. The requirement for regular alcohol intake may also reflect the transient nature of ethanol-induced histone acetylation. Conversely, ethanol may also stimulate carcinogenesis by inhibiting DNA methylation, as it was shown to reduce various pathways leading to DNA and histone methylation. However, unlike acetylation, where ethanol directly increases the substrate for acetylation, this effect was only observed in the high alcohol exposure cohort. While alcohol-derived acetate may be beneficial for health after midlife, various detrimental effects of alcohol consumption remain, and hence, we do not advocate excessive drinking to increase acetate. This opinion article establishes a possible role of ethanol-derived acetate in achieving homeostasis and sustaining an organism's health span. • Alcohol-derived acetate and maintenance of histone acetylation may be a major driver of health and lifespan extension. • As acetyl-coA level drop with age, the positive effects of ethanol-derived acetate may be more pronounced after midlife. • The detrimental effects of Alcohol on DNA methylation are only observed during chronic high dose exposure. [ABSTRACT FROM AUTHOR]

As the percentage of the global population over age 65 grows, and with it a subpopulation of individuals with alcohol use disorder (AUD), understanding the effect of alcohol on the aged brain is of utmost importance. Neuroinflammation is implicated in both natural aging as well as alcohol use, and its role in alterations to brain morphology and function may be exacerbated in aging individuals who drink alcohol to excess. The neuroimmune response to alcohol in aging is complex. The few studies investigating this issue have reported heightened basal activity and either hypo- or hyper-reactivity to an alcohol challenge. This review of preclinical research will first introduce key players of the immune system, then explore changes in neuroimmune function with aging or alcohol alone, with discussion of vulnerable brain regions, changes in cytokines, and varied reactions of microglia and astrocytes. We will then consider different levels of alcohol exposure, relevant animal models of AUD, and neuroimmune activation by alcohol across the lifespan. By identifying key findings, challenges, and targets for future research, we hope to bring more attention and resources to this underexplored area of inquiry. • Both alcohol and aging elicit an array of changes to the neuroimmune environment. • Microglial and astrocytic response to alcohol and aging is multi-faceted and dynamic. • Context is key – duration, amount, and route of alcohol exposure, species/strain. [ABSTRACT FROM AUTHOR]

There is growing interest in understanding how ethanol use interacts with advancing age to influence the brain and cognition. Animal models are employed to investigate the cellular and molecular mechanisms of brain aging and age-related neurodegenerative diseases that underlie cognitive decline. However, all too often research on problems and diseases of the elderly are conducted in healthy young animals, providing little clinical relevance. The validity of animal models is discussed, and confounds due to age-related differences in anxiety, sensory-motor function, and procedural learning are highlighted in order to enhance the successful translation of preclinical results into clinical settings. The mechanism of action of ethanol on brain aging will depend on the dose, acute or chronic treatment, or withdrawal from treatment and the age examined. Due to the fact that humans experience alcohol use throughout life, important questions concern the effects of the dose and duration of ethanol treatment on the trajectory of cognitive function. Central to this research will be questions of the specificity of alcohol effects on cognitive functions and related brain regions that decline with age, as well as the interaction of alcohol with mechanisms or biomarkers of brain aging. Alternatively, moderate alcohol use may provide a source of reserve and resilience against brain aging. Longitudinal studies have the advantage of being sensitive to detecting the effects of treatment on the emergence of cognitive impairment in middle age and can minimize effects of stress/anxiety associated with the novelty of alcohol exposure and behavioral testing, which disproportionately influence aged animals. Finally, the effect of alcohol on senescent neurophysiology and biomarkers of brain aging are discussed. In particular, the interaction of age and effects of alcohol on inflammation, oxidative stress, N-methyl- d -aspartate receptor function, and the balance of excitatory and inhibitory synaptic transmission are highlighted. • An overview of validity of animal models for examining alcohol effects on brain aging is provided. • Advantages of longitudinal studies for minimizing confounds are discussed. • Specificity of effects on cognitive function and related brain regions are discussed. • Alcohol effects on senescent neurophysiology and biomarkers of brain aging are discussed. • Alcohol may affect susceptibility to brain aging or reserve and resilience. [ABSTRACT FROM AUTHOR]

Alcohol (ethanol) is among the most popularly consumed beverages globally. Ethanol was earlier demonstrated to elicit cognitive impairment and depressive-like effects in both human and animal studies. Rutin (R) is known for its antioxidant, anti-inflammatory, immunomodulatory, and anti-depressive properties, among others. Herein, we investigate the impact of rutin on ethanol-induced cognitive impairment and depressive-like effects in rats and the involvement of the indoleaminergic pathway. Three groups of eight rats each were orally exposed to drinking water (group 1), ethanol (5 g/kg body weight)-group 2 (via oral gavage), and ethanol + R (5 g/kg body weight + 50 mg/kg body weight)-group 3 (via oral gavage) for 35 days. Results showed that exposure to ethanol significantly (p < 0.0001) reduced spontaneous alternation in the Y-maze and increased immobility time in the tail suspension test (TST), which indicates cognitive impairment and depressive-like behavior in rats. We observed increased IDO activity/expression, and inflammatory responses, with attendant disruption in antioxidant systems and concomitant elevation in malondialdehyde (MDA) levels in the cerebral cortex and hippocampus. Following rutin co-exposure, an ethanol-mediated increase in indoleamine 2,3-dioxygenase [IDO] activity/expression and decrease in antioxidant enzymes, in addition to an increase in markers of inflammatory response and MDA production, was significantly (p < 0.0001) prevented compared with controls. Additionally, altered behavioral indices were prevented by rutin co-exposure. Taken together, these findings reveal the involvement of the indoleaminergic pathway in rutin preventive influence against ethanol-induced cognitive impairment and depressive-like behavior in rats. • Alcohol consumption elicited neurobehavioral impairments in the male rat. • Rutin prevented ethanol-induced neurobehavioral deficits. • Rutin diminished oxidative stress and inflammatory biomarkers induced by ethanol. • Rutin prevented ethanol-induced activation of IDO activities/expression. • Rutin may represent a possible therapeutic agent against ethanol-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

After an extended alcohol-drinking history, alcohol use can transition from controlled to compulsive, causing deleterious consequences. Alcohol use can be segregated into two distinct behaviors, alcohol seeking and alcohol taking. Expression of habitual and compulsive alcohol seeking depends on the dorsolateral striatum (DLS), a brain region thought to engage after extended alcohol access. However, it is unknown whether the DLS is also involved in compulsive-like alcohol taking. The purpose of this experiment was to identify whether the DLS gates compulsive-like binge alcohol drinking. To ask this question, we gave adult male and female C57BL/6J mice a binge-like alcohol-drinking history, which we have previously demonstrated to produce compulsive-like alcohol drinking (Bauer, McVey, & Boehm, 2021), or a water-drinking history. We then tested the involvement of the DLS on gating binge-like alcohol drinking and compulsive-like quinine-adulterated alcohol drinking via intra-DLS AMPA receptor antagonism. We hypothesized that pharmacological lesioning of the DLS would reduce compulsive-like quinine-adulterated alcohol (QuA) drinking, but not non-adulterated alcohol drinking, in male and female C57BL/6J mice. Three important findings were made. First, compulsive-like alcohol drinking is significantly blunted in cannulated mice. Because of this, we conclude that we were not able to adequately assess the effect of intra-DLS lesioning on compulsive-like alcohol drinking. Second, we found that the DLS gates binge-like alcohol drinking initially, which replicates findings in our previous work (Bauer, McVey, Germano, Zhang, & Boehm, 2022). However, following an extended alcohol history, the DLS no longer drives this behavior. Finally, alcohol and QuA front-loading is DLS-dependent in alcohol-history mice. Intra-DLS NBQX altered these drinking behaviors without altering ambulatory locomotor activity. These data demonstrate the necessity of the DLS in binge-like alcohol drinking before, but not following, an extended binge-like alcohol-drinking history and in alcohol front-loading in alcohol-history mice. [ABSTRACT FROM AUTHOR]

A symptom of alcohol use disorder (AUD) is compulsive drinking, or drinking that persists despite negative consequences. In mice, aversion-resistant models are used to model compulsive-like drinking by pairing the response for alcohol with a footshock or by adding quinine, a bitter tastant, to the alcohol solution. crossed High Alcohol Preferring (cHAP) mice, a selectively bred line of mice that consumes pharmacologically relevant levels of alcohol, demonstrate a high level of aversion-resistance to quinine-adulterated alcohol. The current study investigated quinine-resistant and footshock-resistant responding for 10% ethanol in male and female cHAP mice with vs. without a history of alcohol exposure. cHAP mice were first trained to respond for 10% ethanol in an operant-response task. Next, mice were exposed to water or 10% ethanol for twelve 24-h sessions using a two-bottle choice procedure. Footshock-resistant ethanol responding was then tested in the operant chamber by pairing a footshock (0.35 mA) with the nose-poke response during one session. Quinine-resistant responding for alcohol was tested over five sessions (500-2500 μM quinine). Finally, footshock sensitivity was assessed using a flinch, jump, vocalize test. Alcohol exposure history did not influence responses for 10% ethanol or either measure of aversion-resistance. Further, cHAP mice were sensitive to footshock punishment but continued to respond for alcohol at all quinine concentrations. No sex differences were observed in any measure of alcohol responding, but female cHAP mice were less sensitive to footshock than males. These results replicate and extend the previous demonstration of a robust, innate resistance to quinine aversion in cHAP mice and further suggest that this tendency is not observed when footshock is used to punish drinking. [ABSTRACT FROM AUTHOR]

Initiating alcohol use in adolescence significantly increases the likelihood of developing adult alcohol use disorder (AUD). However, it has been difficult to replicate adolescent alcohol exposure leading to increased adult alcohol intake across differing preclinical models. In the present study, differentially housed male rats (group vs. single cages) were used to determine the effects of voluntary intermittent exposure of saccharin-sweetened ethanol during adolescence on adult intake of unsweetened 20% ethanol. Adolescent male rats were assigned to group- or isolated-housing conditions and underwent an intermittent 2-bottle choice in adolescence (water only or water vs. 0.2% saccharin/20% ethanol), and again in adulthood (water vs. 20% ethanol). Intermittent 2-bottle choice sessions lasted for 24 h, and occurred three days per week, for five weeks. Rats were moved from group or isolated housing to single-housing cages for 2-bottle choice tests and returned to their original housing condition on off days. During adolescence, rats raised in isolated-housing conditions consumed significantly more sweetened ethanol than rats raised in group-housing conditions, an effect that was enhanced across repeated exposures. In adulthood, rats raised in isolated-housing conditions and exposed to sweetened ethanol during adolescence also consumed significantly higher levels of unsweetened 20% ethanol compared to group-housed rats. The effect was most pronounced over the first five re-exposure sessions. Housing conditions alone had little effect on adult ethanol intake. These preclinical results suggest that social isolation stress, combined with adolescent ethanol exposure, may play a key role in adult AUD risk. [ABSTRACT FROM AUTHOR]