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Adolescent intermittent ethanol (AIE) exposure in rodents has been shown to alter adult behavior in several domains, including learning and memory, social interaction, affective behavior, and ethanol self-administration. AIE has also been shown to produce non-specific behavioral changes that compromise behavioral efficiency. Many studies of these types rely on measuring behavior in mazes and other enclosures that can be influenced by animals' activity levels and exploratory behavior, and relatively few such studies have assessed sex as a biological variable. To address the effects of AIE and its interaction with sex on these types of behavioral assays, male and female adolescent rats (Sprague Dawley) were exposed to 10 doses of AIE (5 g/kg, intra-gastrically [i.g.]), or control vehicle, over 16 days (postnatal day [PND] 30-46), and then tested for exploratory and anxiety-like behaviors on the novelty-induced hypophagia (NIH) task in an open field, the elevated plus (EPM) maze, and the Figure 8 maze. AIE reduced activity/exploratory behaviors in males on the anxiety-producing NIH and EPM tasks, but reduced activity in both males and females in the Figure 8 maze, a task designed to create a safe environment and reduce anxiety. Independent of AIE, females engaged in more rearing behavior than males during the NIH task but less in the EPM, in which they were also less active than males. AIE also increased EPM open arm time in females but not in males. These findings demonstrate previously unrecognized sex differences in the effects of AIE on activity, exploratory behavior, and anxiety-like behavior; additionally, they underscore the need to design future behavioral studies of AIE using sex as a variable and with rigorous attention to how AIE alters these behaviors.

BACKGROUND: Anxiety disorder is one of the most common psychiatric problems. Prolonged stress gives rise to anxiety-like behavior in animals. Environmental interventions influence the outcome of anxiety treatment. Environmental enrichment (EE) can modulate brain’s structure and function. AIM: The objective of the study was to evaluate EE effects on anxiety-like behavior and corticosterone (CORT) level after unpredictable chronic mild stress (UCMS). METHODS: A total of 28 rats were assigned into four groups randomly: Control, UCMS, UCMS+EE, and UCMS+fluoxetine. UCMS, EE, and fluoxetine were given for 21 days. Anxiety behavior was measured on day 22nd using Elevated Plus Maze. Behavioral measurement was based on the total time spent and total entries onto open and closed arms. CORT was measured using ELISA. RESULTS: UCMS increased anxiety-like behavior as seen from reduced number of entries and time spent in open arms as well as increased number of entries and time spent in in closed arms in UCMS group than control. Rats in EE group spent more time and made more entries in the open arms than UCMS group (both p = 0.002). Anxiolytic effect of EE was stronger than fluoxetine. Plasma CORT level among groups did not differ significantly (p = 0.351). CONCLUSION: EE can ameliorate stress-induced anxiety-like behavior without affecting CORT level.

Aims: Adenia lobata (Jacq.) Engl. (Passifloraceae) is widely used in Ivorian traditional pharmacopeia to heal various chronic diseases, relieve headache and pain of gingiva inflammation, and facilitate labor. Here, we investigated the effects of hydroethanolic extract Adenia lobata (HEAL) on nociceptive pain and subsequent anxiety-like behavior. Materials and Methods: We used several experimental pain tests as the writhing, formalin and hot plate to evaluate both antinociceptive and anti-inflammatory actions of the extract. Anxiety related to nociception was tested with open field and elevated plus maze tests. Then, mice were sacrificed for assessing some oxidative stress markers. Results: The extract of 30 mg/kg, p.o. reduced in the similar manner as reference peripheral drug salcylicacetic acid (ASA, 200 mg/kg, i.p.) the number of writhings induced by acid acetic. In both neurogenic and inflammatory phases of formalin test, the extract demonstrated an effective antinociceptive activity than ASA, but comparable to central analgesic tramadol (50 mg/kg, i.p). However, Adenia lobata reduced lesser thermal-induced pain than tramadol in hot plate test, but significantly compared to ASA. Furthermore, HEAL altered anxiety-like behavior in each case of the pain condition studied. Also, the extract showed the highest antioxidant activity by reduction oxide nitric (NO) and malondialdehyde (MDA), and increase non protein thiol (NP-SH) levels. Conclusion: In conclusion, HEAL possesses antinociceptive and anti-inflammatory actions on peripheral and central mechanisms of pain. The phytochemicals components of the extract as alkaloids and flavonoids suggest to interact with the opioid system and combat the oxidative stress, respectively. Our findings provide scientific basis for the use of Adenia lobata in traditional medicine against pain and related diseases.

Introduction: Depression and anxiety are the most common psychiatric disorders. These conditions widely occur in industrial societies and severely affect individuals’ lives. N-Acetylcysteine (NAC) is a mucolytic compound with antioxidant and anti-inflammatory effects. This study aimed to investigate the potential therapeutic effects of NAC on chronic noise-induced depression- and anxiety-like behaviors in mice. Methods: Fifty male BALB/c mice were randomly divided into 5 groups, as follows: control, noise90 dB, noise110 dB, noise 90+NAC, and noise 110+NAC groups. Animals in the noise groups were exposed to 90 dB 2 h/day and 110 dB 2 h/day for 30 days. The NAC groups received NAC (325 mg/kg P.O.) 20 min after being exposed to noise. To evaluate depressive- and anxiety-like behaviors, the examined mice were subjected to the Open Field Test (OFT), Sucrose Preference Test (SPT), Tail Suspension Test (TST), and Elevated Plus Maze (EPM) tasks. At the end of the behavioral tests, the study animals were sacrificed. Accordingly, the levels of Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were determined in the Hippocampus (HIP) and the Prefrontal Cortex (PFC). Results: The obtained results suggested that noise exposure would induce anxiety- and depressive-like behaviors, being reversed by NAC administration. Moreover, chronic administration of NAC significantly increased antioxidant enzyme activities and reduced lipid peroxidation (MDA levels) in the PFC and HIP of noise-exposed mice. Conclusion: Our findings revealed that administrating NAC would reduce the adverse effects of noise on the brain and would exert anti-depressant and anxiolytic effects

Introduction:Achillea tenuifolia Lam ( AT) has several biological activities and medicinal properties. In this study, we elucidated the impact of the AT on anxiety-related behaviors, reproductive parameters, antioxidant capacity in male rats subjected to chronic restraint stress (CRS).Methods:35 Wistar rats were divided into five groups: control, CRS-control (received normal saline) and three CRS-treated groups received AT extract (100, 150, and 200 mg/kg body weight) for 21 consequences days. To induce CRS rats, the rats were immobilized for 21 days and received the extract orally. On the last day of treatment, anxiety-related behaviors were assessed through the sucrose preference test (SPT) as well as elevated plus maze (EPM) tests. Corticosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH), testosterone levels were evaluated to determine reproductive capacity. Sperm parameters including the total count, motility, and viability were also analyzed. Weight of body, testis and seminal vesicles was measured as well.Results:The findings revealed that 100, 150, and 200 mg/kg of AT extract had anxiolytic effects in CRS rats, as confirmed by the EPM test and SPT. In addition, AT extract could improve fertile capacity and sperm quality to varying degrees. The level of corticosterone had decreased, whereas the level of LH, FSH and testosterone had increased in CRS-treated rats. Moreover, the reduced level of MDA coincided with an increased rate of antioxidant capacity. Our findings suggest that AT extract could alleviate stress-induced dysfunctions.Conclusion:Overall, these observations would infer that AT extract could improve fertility capacity and behavioral impairment in the stress conditions.Graphical abstract:Assumption pathway describing the probability underlying mechanism of CRS-induced anxiety and reproductive toxicity and protective effect of AT.

Anxiety, a negative state of high arousal and vigilance, is especially prevalent in women, making identification of underlying mechanisms critical for developing effective therapies. With the challenge of disentangling biological and social factors in humans, animal tests can provide valuable insights, although such tests, developed in males, have unclear validity for females. To better understand patterns of sex differences across multiple measures within two classical rodent anxiety tests. We examined female and male adult Wistar rats (n = 15–18/group) that were single-housed in the novelty suppression of feeding test (NSFT) that involves food under a bright light in food-restricted animals, and light–dark test (LDT), which reflects innate aversion to bright light. To further validate these tests in females, we also examined the impact of 1 mg/kg diazepam. NSFT measures of the most direct interaction with food, latency to grab food and food consumed, indicated increased anxiety-like behavior in females versus males, with diazepam altering these behaviors in females but not males. Most other measures showed more similar effects of diazepam across the sexes, with some evidence of reduced anxiety-like behavior in LDT for females. Principal component analyses indicated limited relationships across behavioral factors, underscoring previous suggestions of the importance of assessing multiple measures to maximize information and ethological relevance. Combining our findings and previous studies, we speculate that increased anxiety-like behavior in females manifests especially when there is a specific, life-relevant condition (e.g., food in the NSFT). Our findings also validate NSFT and LDT use in females.

Various animal models of anxiety have been developed to evaluate anxiety and anxiolytic drugs. However, non-uniform measuring paradigms, variability in apparatus use and individual differences in animals confound study results. In this study, when all animals were included in the data analysis, we found no significant differences between control and stressed mice using standard behavioral paradigms for assessing anxiety (elevated plus maze and open field test). To provide a better assessment of anxiety, we therefore used a machine learning approach to analyze the behavioral patterns of each animal, and selected typical subjects in each group for use as a training set according to classical anxiety parameters. Spontaneous behaviors in these animals were captured by multi-view cameras and decomposed into sub-second modules using Behavior Atlas, and six behavioral features providing statistically significant difference between stressed and control mice were identified. Combined with low-dimensional embedding and clustering, new features were used to discriminate stressed mice from controls, in both the training set and all objects. Our results show Behavior Atlas is a powerful approach for identifying new potential biomarkers in an unbiased fashion. Our approach can complement classical measuring paradigms to objectively and comprehensively evaluate anxiety-like behaviors.

Background: Diabetes can impair cognitive performance and lead to dementia. Patients with type 1 diabetes mellitus (T1DM) are reported with different levels of cognitive dysfunctions in various cog...

Both the noradrenergic and galaninergic systems have been implicated in stress-related neuropsychiatric disorders, and these two neuromodulators are co-released from the stress-responsive locus coeruleus (LC); however, the individual contributions of LC-derived norepinephrine (NE) and galanin to behavioral stress responses are unclear. Here we aimed to disentangle the functional roles of co-released NE and galanin in stress-induced behavior. We used foot shock, optogenetics, and behavioral pharmacology in wild-type (WT) mice and mice lacking either NE (Dbh(−/−)) or galanin (Gal(cKO-Dbh)) specifically in noradrenergic neurons to isolate the roles of these co-transmitters in regulating anxiety-like behavior in the elevated zero maze (EZM) either immediately or 24 h following stress. Foot shock and optogenetic LC stimulation produced immediate anxiety-like behavior in WT mice, and the effects of foot shock persisted for 24 h. NE-deficient mice were resistant to the anxiogenic effects of acute stress and optogenetic LC stimulation, while mice lacking noradrenergic-derived galanin displayed typical increases in anxiety-like behavior. However, when tested 24 h after foot shock, both Dbh(−/−) and Gal(cKO-Dbh) mice lacked normal expression of anxiety-like behavior. Pharmacological rescue of NE, but not galanin, in knockout mice during EZM testing was anxiogenic. In contrast, restoring galanin, but not NE, signaling during foot shock normalized stress-induced anxiety-like behavior 24 h later. These results indicate that NE and noradrenergic-derived galanin play complementary, but distinguishable roles in behavioral responses to stress. NE is required for the expression of acute stress-induced anxiety, while noradrenergic-derived galanin mediates the development of more persistent responses following a stressor.

Curcuma longa (C. longa), also known as curcumin, is a lipophilic polyphenol substance proven to have cholesterol-lowering, anti-diabetic, anti-inflammatory, anti-oxidant, and anti-cancer properties in both in vitro and in vivo models. Most previous studies investigated the effect of C. longa on diabetic mice and therefore, there is a need to investigate the effect of C. longa on normoglycemic mice. Depression is a common consequence of anxiety that affects 21% of the world’s population. Since the prevalence of diabetes and depression is on the rise globally, it is important to search for safer and cost-effective management for these disorders. In doing so, it is therefore essential to investigate its effect in normoglycemic mice. The current study determines the effect of C. longa on blood glucose level and anxiety-like behavior in normoglycemic Swiss albino mice. A total of 20 mice were divided into four groups of five (n=5 per group). Group I (control) received distilled water 10 ml/kg, groups II, III, and IV received C. longa at 5%, 10%, and 20%, respectively, for 14 days. We found that 20% C. longa group showed a significant (p0.05) difference in both fasting blood glucose level and anxiety-like behavior between the mice treated with 5% and 10% C. longa and the control group. This study indicates that C. longa at high concentration is unsafe for consumption by normoglycemic Swiss albino mice.

Objective In this study, we evaluated the effect of neonatal ketamine exposure on anxiety-like and exploratory behaviours in adult the Balb/c and C57BL/6 strains of mice which anxiety responses are different. Methods Ketamine was administered at two different doses single dose (10, 20 mg/kg, 0.1 ml/10 g body weight, intraperitoneally) and repeated doses (10, 20 mg/kg every 240 minutes; thrice times) on the 7th postnatal day to male Balb/c and C57BL/6 mice. In adulthood, open-field (OF) and elevated plus maze (EPM) apparatuses were used to evaluate exploratory and anxiety-like behaviour. Results In the C57BL/6 mice, the 20 mg/kg single dose decreased open-arm time and total-arm entries in EPM and increased time of central latency and decreased distance travelled in OF. Both the 10 and 20 mg/kg repetitive doses increased time of central latency and decreased time spent in the centre, frequency of rearing and centre crossing in OF and decreased open-arm time, total-arm entries, number of open-arm entries in EPM. The 20 mg/kg repetitive dose decreased number of head dipping behaviours in EPM. In the Balb/c mice, both the single and repetitive 10-20 mg/kg doses had no significant effect on anxiety-like and exploratory behaviours. Conclusion There were no significant differences in anxiety-like and exploratory behaviour in different strains by the single 10 mg/kg dose. However, in the C57BL/6 mice, both the single and repetitive 20 mg/kg doses and the 10 mg/kg repetitive dose increased anxiety-like behaviour and decreased exploratory behaviour in EPM and OF. In conclusion, hereditary factors may be effective on the effect of neonatal ketamine treatment on anxiety-like and exploratory behaviour.

Environmental enrichment for mice lags behind the standard enrichment offered to other laboratory rodents due to concerns about environmental variability and, in specific contexts, aggression. Our objective in this study was to evaluate concerns that the introduction of structural enrichment in the form of a single red acrylic mouse tunnel into murine housing may confound study findings. We measured effects on anxiety-like behaviors (elevated zero maze and open field activity), hippocampal neurogenesis, body weight gain, and physiologic markers of stress (adrenal gland weight, plasma corticosterone concentration, and neutrophil:lymphocyte ratio). Male and female C57BL/6J mice were randomly assigned to one of 2 groups: a standard-housed control group with enrichment consisting of paper nesting material, or an enriched group that received a single acrylic tunnel in addition to nesting material. All results fell within biologically normal ranges regardless of treatment, and variability (standard deviation) was not significantly different between groups for any measure. Mice in the enriched group showed modest differences during open field testing suggestive of decreased anxiety, traveling farther and depositing fewer fecal boli than standard-housed mice. Male mice in the tunnel-enriched group gained more body weight than standard-housed male mice. No significant effects by treatment were found in neurogenic or physiologic parameters. These results indicate that provision of simple structural enrichment is unlikely to have confounding effects on murine anxiety-like behaviors, neurogenesis, body weight gain, or physiologic parameters. We therefore recommend the inclusion of simple structural enrichment, such as an acrylic tunnel, to the standard environmental enrichment of social housing and nesting material for mice.

Abstract Rationale Adolescents represent a vulnerable group due to increased experimentation with illicit substances that is often associated with the adolescent period, and because adolescent drug use can result in long-term effects that differ from those caused by drug use initiated during adulthood. Objectives The purpose of the present study was to determine the effects of repeated heroin vapor inhalation during adolescence on measures of nociception, and anxiety-like behavior during adulthood in female and male Wistar rats. Methods Rats were exposed twice daily to 30 min of heroin vapor from post-natal day (PND) 36 to PND 45. At 12 weeks of age, baseline thermal nociception was assessed across a range of temperatures with a warm-water tail-withdrawal assay. Anxiety-like behavior was assessed in an elevated plus-maze (EPM) and activity was measured in an open-field arena. Starting at 23 weeks of age, baseline thermal nociception was re-assessed, nociception was determined after acute heroin or naloxone injection, and anxiety-like behavior was redetermined in the EPM. Results Adolescent heroin inhalation altered baseline thermal nociception in female rats at 12 weeks of age and in both female and male rats at ~ 23 weeks. Heroin-treated animals exhibited anxiety-like behavior when tested in the elevated plus-maze, showed blunted heroin-induced analgesia, but exhibited no effect on naloxone-induced hyperalgesia. Conclusions The present study demonstrates that heroin vapor inhalation during adolescence produces behavioral and physiological consequences in rats that persist well into adulthood.

Aims Alcohol exposure during adolescence is associated with both increased risk for alcohol use disorders and anxiety in adulthood. Our present experiments examined this association using alcohol-preferring AA (Alko Alcohol) rats selected for high voluntary alcohol drinking. Methods Two groups of female AA rats acquired alcohol drinking at different ages. We gave the adolescent-onset group free choice to 10% alcohol and water for seven weeks, starting on post-natal day 42 (PND 42), whereas the adult-onset group started drinking alcohol on PND 112. After the 7-week drinking, we withdrew the adolescent group from alcohol for two weeks, followed by another voluntary 7-week drinking period, started at the same age as the adult-onset group. We assessed anxiety-like behaviour repeatedly during alcohol drinking with open field and elevated plus maze tests. At the end of alcohol drinking, we also tested the rats using the light/dark box, stress-induced body temperature test and social dominance test. Results During the first 7-week alcohol drinking, adolescent rats exhibited significantly slower acquisition of alcohol drinking and lower alcohol preference than the adult-onset group. However, when tested at the same age as the adult-onset rats, they displayed identical alcohol intake and preference. We found no alcohol-induced effects on anxiety- or stress-related behaviour in the experimental groups at any time points. Conclusions These data show that the genetically determined phenotype of high alcohol drinking of the female alcohol-preferring AA rats is not associated with a predisposition to develop anxiety-like behaviour following voluntary alcohol exposure, even when initiated during adolescence.

New findings What is the central question of this study? What is the effect in male and female offspring of a protein-deficient diet producing intrauterine growth restriction (IUGR) in maternal mice on morphometric, metabolic and behavioural parameters before and after a challenge with a fat diet? What is the main finding and its importance? Male and female mice presented different growth trajectories after birth. IUGR favoured increased adiposity in male mice, and high-fat diet-induced anxiety-like behaviour in female mice. Abstract As there is sexual dimorphism in the response to maternal manipulations, we aimed to analyse the effects of intrauterine growth restriction (IUGR) in both sexes on morphometric, metabolic and behavioural parameters throughout postnatal development, and after challenge with a hyperlipidic diet. Female Swiss mice (n = 59) were distributed into two groups (SD: standard diet, n = 26; and PDD: isocaloric protein-deficient diet, n = 33), 2 weeks before mating and during the gestational period. After birth, offspring from SD and PDD dams were cross-fostered and nurtured by SD dams until postnatal day (PND) 28. At PND 60 all animals were challenged with a hypercaloric diet for 4 weeks. Offspring birth weight was significantly reduced in the PDD group compared to the SD group (P = 0.0001), but only male offspring presented a rapid catch-up during the first 21 days of development. Although no differences in body weight were observed between groups after the challenge with the hyperlipidic diet, an increase in the relative perigonadal white adipose tissue (P = 0.009) and a decrease in gross gastrocnemius muscle weight (P = 0.010) were observed in the PDD males. In relation to behavioural tests, there was an increase in locomotion in both sexes (P = 0.0001), and a decrease in female grooming (P = 0.006) in the PDD group. Additionally, females from the PDD group showed increased hyperlipidic food intake. In conclusion, IUGR affected both sexes, with females showing prominent behavioural modifications and males presenting altered body composition elicited by a hyperlipidic diet.

Risk-taking behaviors are a primary contributor to elevated adolescent injury and mortality. Locomotor and anxiety-like behaviors in rodents have been used to examine risk-taking. Here, we examined risk-taking behavior (i.e., changes in locomotor and anxiety-like behaviors) from early to late adolescence and adulthood in male and female rats in the open-field (OF) apparatus and the light-dark (LD) test. We also examined whether these behaviors are affected by an early adolescent immune stressor, lipopolysaccharide (LPS). Long-Evans male and female rats were injected with LPS (200 μg/kg) or vehicle control in early adolescence (postnatal day [PND] 30 and 32). Anxiety-like behavior and locomotor activity were measured in early (PND 38-40), late adolescence (PND 50), and adulthood (PND 88 and 98) in the OF and in early adolescence (PND 42) and adulthood (PND 90) in the LD test. Early and late adolescent rats displayed significantly greater locomotor and anxiety-like behaviors than adult rats in the OF and LD test. Sex differences were also found, with adolescent and adult females displaying greater locomotor and anxiety-like behaviors than male rats in the OF and LD tests. LPS administered two times in early adolescence did not have a significant impact on either locomotor or anxiety-like behaviors suggesting minimal impact of the immune stressor.

Sex differences in anxiety-related behaviours have been documented in many animals and are notable in human populations. A major goal in behaviour research is to understand why and how sex differences in cognitive-emotional states like anxiety arise and are regulated throughout life. Anxiety allows individuals to detect and respond to threats. Mating is a candidate regulator for anxiety because threats are likely to change, often in sex-specific ways, when individuals shift to a postmating reproductive state. However, we know little about how mating mediates anxiety-related behaviour in males and females, or about how males might influence female anxiety via seminal proteins transferred during mating. To address this gap, we examined anxiety-related behaviour in the fruit fly Drosophila melanogaster, an emerging model animal for anxiety, with respect to sex, mating and sex peptide, a seminal protein known to modulate a host of female postmating responses in fruit flies. We assayed anxiety-like behaviour using the open-field assay to assess individual avoidance of the interior of an arena (‘wall-following’ behaviour). We found sex differences in activity level, but no evidence for sex differences in wall-following behaviour. We found no effects of mating in either sex, or of the presence of the sex peptide receptor in females, on wall following. Our results suggest that anxiety is not one of the cognitive-emotional states regulated by mating and sex peptide in fruit flies, and that researchers need an alternative model for sex differences in anxiety.

We recently found that adolescent cocaine exposure (ACE) resulted in an enhancement of the γ-aminobutyric acid (GABA) neurotransmitter system in the prelimbic cortex (PrL) of adult mice. Here, we aim to further investigate the role of GABAergic transmission, especially parvalbumin (PV) interneurons within PrL in the development of ACE-induced anxiety-like behavior, and to assess whether and how electro-acupuncture (EA) therapeutically manage the ACE-induced abnormal behaviors in adulthood. ACE mice exhibited the enhanced anxiety-like behaviors in their adulthood, accompanied by increased GABAergic transmission and PV interneurons in PrL. Chemogenetic blocking PV interneurons in PrL alleviated ACE-enhanced anxiety-like behaviors in mice. Importantly, 37-day EA treatments (mixture of 2 Hz/100 Hz, 1 mA, 30 minutes once a day) at the acupoints of Yintang (GV29) and Baihui (GV20) also alleviated ACE-induced anxiety-like behaviors, and rescued ACE-impaired GABAergic neurotransmitter system and PV interneurons in PrL. In parallel, EA treatments further suppressed the activities of pyramidal neurons in PrL, suggesting that EA treatments seem to perform it beneficial effects on the ACE-induced abnormal emotional behaviors by "calming down" the whole PrL. Collectively, these findings revealed that hyper-function of GABAergic transmission, especially mediating by PV interneurons in PrL may be key etiology underlying ACE-induced anxiety-like behaviors. At least by normalizing the function of GABAergic and PV interneurons, EA may represent a promising therapeutic strategy for managing adolescent substance use-related emotional disorders.

Exposure to stress during early life affects subsequent behaviors and increases the vulnerability to adult pathologies, a phenomenon that has been well documented in humans and rodents. In this study, we introduce a chronic unpredictable stress protocol adapted to young zebrafish, which is an increasingly popular vertebrate model in neuroscience research. We exposed zebrafish to a series of intermittent and unpredictable mild stressors from day 10 to 17 post-fertilization. The stressed fish showed a reduced exploration of a novel environment one day post-stress and an increased responsiveness to dark-light transition two days post-stress, indicative of heightened anxiety-related behaviors. The stress-induced decrease in exploration lasted for at least three days and returned to control levels within one week. Moreover, stressed fish were on average 8% smaller than their control siblings two days post-stress and returned to control levels within one week. All together, our results demonstrate that young zebrafish exposed to chronic unpredictable stress develop growth and behavioral alterations akin to those observed in rodent models.

Background: trans-Resveratrol has been extensively investigated for its anti-inflammatory, antioxidant, and anti-psychiatric properties. However, whether it could rescue posttraumatic stress disorder-like stress-induced pain abnormality is unknown. Aim: The present study examined the effects of trans-resveratrol on anxiety-like behavior and neuropathic pain induced by single-prolonged stress, which is a classical animal model for mimicking posttraumatic stress disorder. Methods: The single-prolonged stress-induced anxiety-like behavior and pain response were detected by the novelty suppressed feeding, marble burying, locomotor activity, von Frey, and acetone-induced cold allodynia tests in mice. The serum corticosterone levels and glucocorticoid receptor, protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression were detected by enzyme-linked immunosorbent assay and immunoblot analyses. Results: trans-Resveratrol reversed single-prolonged stress-induced increased latency to feed and the number of marbles buried in the novelty suppressed feeding and marble burying tests, but did not significantly influence locomotion distance in the locomotor activity test. trans-Resveratrol also reversed single-prolonged stress-induced cold and mechanical allodynia. Moreover, single-prolonged stress induced abnormality in the limbic hypothalamus-pituitary-adrenal axis was reversed by trans-resveratrol, as evidenced by the fact that trans-resveratrol reversed the differential expression of glucocorticoid receptor in the anxiety- and pain-related regions. In addition, trans-resveratrol increased protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels, which were decreased in mice subjected to single-prolonged stress. Conclusions: These results provide compelling evidence that trans-resveratrol protects neurons against posttraumatic stress disorder-like stress insults through regulation of limbic hypothalamus-pituitary-adrenal axis function and activation of downstream neuroprotective molecules such as protein kinase A, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor expression.

Many neuropsychiatric disorders are associated with both dopaminergic (DAergic) and developmental hypotheses. Since DAergic receptors are expressed in the developing brain, it is possible that alterations in dopamine (DA) signaling may impair brain development and consequent behavior. In our previous study, using a zebrafish model, we showed that an increase of DA during the 3 to 5 days postfertilization (dpf) developmental window (an important window for GABAergic neuronal differentiation) affects the motor behavior of 5 dpf larvae. In this study, we set out to determine whether these behavioral alterations were sustained in larvae at older stages (7 and 14 dpf). To test this hypothesis, we chronically treated zebrafish larvae from 3 to 5 dpf with DA. After washing the drug, we recorded and analyzed the first 5 and 30 min of the motor behavior of 5, 7, and 14 dpf subjects. We analyzed mobile episodes, distance traveled, time mobile, distance traveled per mobile episode, time in movement per mobile episode, and distance traveled per time mobile. We showed, once again, that an increase of DA during the 3 to 5 dpf developmental window reduces the number of movement episodes initiated by 5 dpf larvae. We also detected a decrease of other motor behavior parameters in 5 dpf DA-treated larvae. We observed that these alterations are sustained in the 7 dpf larvae. However, we did not see these general locomotor alterations in the 14 dpf larvae. Moreover, we detected a decrease of distance traveled and an increase of time of locomotion per episode in the first 5 min of behavioral analyses in 14 dpf DA-treated larvae. To test if the alterations in the first 5 min were due to anxiety-like behavior, we used a light/dark preference paradigm. We recorded 5dpf, 7dpf, and 14dpf larvae for 5 min and analyzed time of freezing, preference for light or dark, number of entries to the dark, percentage of time in the light. We observed that 5dpf larvae treated with DA showed more freezing, less passages to the dark, and more time spent in the light as compared to their control counterparts. But 7dpf and 14dpf larvae did not show these alterations. Taken overall, therefore, our results suggest that DA does play a role in the development of zebrafish motor behavior, and, furthermore, that some behaviors are more sensitive than others to the effects of DAergic imbalances during development.

Anxiety disorders appear to involve distinct neurobiological mechanisms and several medications are available against this mental health problem. However, pharmacological therapeutic approaches dis...

Anxiety has become a highly paramount field of research attention in psychopharmacology today. Sundry studies have shown a nitric oxide role in the regulation of anxiety. The goal of the study was to investigate sodium nitroprusside ability to affect anxiety-like behavior in mice and to compare this effect with the standard anxiolytic drug, diazepam, using both plus maze test and light/dark box test. The results revealed that sodium nitroprusside at a dose of 1 mg/kg had a significant effect on the behavior in both of the elevated plus maze test and light/dark test. However, at higher dose (3 mg/kg), it has significantly increased the anxiogenic-like effect in the light/dark box test. Diazepam at a dose of 2 mg/kg increased the time spent in open arms in elevated plus maze test and that in light chambers of light/dark test. These outcomes suggest that a nitric oxide pathway seems to play an important role in anxiety. Furthermore, sodium nitroprusside at a dose of 1 mg/kg showed a nearly anxiolytic ability, when compared with diazepam.

Subclinical hypothyroidism tends to be more prevalent due to having a deficiency in iodine intake, which could lead to it. The role of sex differentiation in the susceptibility for anxiety-like beh...

Background The inflammation and oxidative stress (OS) have been considered crucial components of the pathogenesis of depression. Edaravone (EDA), a free radical scavenger, processes strong biological activities including antioxidant, anti-inflammatory and neuroprotective properties. However, its role and potential molecular mechanisms in depression remain unclear. The present study aimed to investigate the antidepressant activity of EDA and its underlying mechanisms. Methods A chronic social defeat stress (CSDS) depression model was performed to explore whether EDA could produce antidepressant effects. Behaviors tests were carried out to examine depressive, anxiety-like and cognitive behaviors including social interaction (SI) test, sucrose preference test (SPT), open field test (OFT), elevated plus maze (EPM), novel object recognition (NOR), tail suspension test (TST) and forced swim test (FST). Hippocampal and medial prefrontal cortex (mPFC) tissues were collected for Nissl staining, immunofluorescence, targeted energy metabolomics analysis, enzyme-linked immunosorbent assay (ELISA), measurement of MDA, SOD, GSH, GSH-PX, T-AOC and transmission electron microscopy (TEM). Western blotting (WB) and quantitative real-time polymerase chain reaction (qRT-PCR) detected the Sirt1/Nrf2/HO-1/Gpx4 signaling pathway. EX527, a Sirt1 inhibitor and ML385, a Nrf2 inhibitor were injected intraperitoneally 30 min before EDA injection daily. Knockdown experiments were performed to determine the effects of Gpx4 on CSDS mice with EDA treatment by an adeno-associated virus (AAV) vector containing miRNAi (Gpx4)–EGFP infusion. Results The administrated of EDA dramatically ameliorated CSDS-induced depressive and anxiety-like behaviors. In addition, EDA notably attenuated neuronal loss, microglial activation, astrocyte dysfunction, oxidative stress damage, energy metabolism and pro-inflammatory cytokines activation in the hippocampus (Hip) and mPFC of CSDS-induced mice. Further examination indicated that the application of EDA after the CSDS model significantly increased the protein expressions of Sirt1, Nrf2, HO-1 and Gpx4 in the Hip. EX527 abolished the antidepressant effect of EDA as well as the protein levels of Nrf2, HO-1 and Gpx4. Similarly, ML385 reversed the antidepressant and anxiolytic effects of EDA via decreased expressions of HO-1 and Gpx4. In addition, Gpx4 knockdown in CSDS mice abolished EDA-generated efficacy on depressive and anxiety-like behaviors. Conclusion These findings suggest that EDA possesses potent antidepressant and anxiolytic properties through Sirt1/Nrf2/HO-1/Gpx4 axis and Gpx4-mediated ferroptosis may play a key role in this effect.

Background: Binge alcohol drinking has been characterized as a key feature of alcoholism. The drinking‐in‐the‐dark (DID) preclinical model, a procedure that promotes high levels of ethanol (EtOH) intake in short periods of time, has been extensively used to investigate neuropharmacological and genetic determinants of binge‐like EtOH consumption. Using DID methodology, alcohol‐preferring strains of mice such as C57BL/6J (B6) mice consume enough EtOH to achieve blood concentrations (≥1.0 mg/ml) associated with behavioral intoxication (i.e., motor incoordination). DID procedures typically involve the use of socially isolated animals (single‐housed prior to and during the experiment). Previous research indicates that stress associated with social isolation can induce anxiety‐like behavior and promote increases in EtOH intake. The present study investigates the role of housing conditions in anxiety‐like behavior and binge‐like EtOH intake using a DID procedure. Methods: Male and female B6 mice were isolated or pair‐housed for a period of 6 weeks prior to evaluation of anxiety‐like (elevated plus maze, light and dark box, open field) and drinking (water, 10% sucrose, 10 to 30% EtOH) behavior. In order to measure intake, a variation of the standard DID procedure using a removable, transparent, and perforated plastic barrier strip (designed to temporarily divide the cage in 2) was introduced. This allowed for individual intake records (2‐hour test) of isolated and socially housed animals. Results: Increased anxiety‐like behavior and reduced sucrose consumption were found in isolated mice. The effects of housing conditions on EtOH intake were sex‐ and concentration‐dependent. In male mice, isolation increased 20 and 30% EtOH intake. In females, however, an increased intake of EtOH (30%) was found in socialized animals. No effects of housing or sex were found at EtOH 10%. Conclusions: Together with previous literature, the present study suggests that social isolation can promote anxiety‐associated behavior and produce sex‐dependent changes in binge‐like EtOH consumption.

Background: The inception of highly active antiretroviral therapy (HAART) has changed the management of human immunodeficiency virus (HIV) positive patients, and their life expectancy has improved. However, neurological complications associated with chronic HAART administration has not been fully addressed. Therefore, this study aimed to evaluate the potential benefits of silver nanoparticles (AgNPs) conjugates on the anxiogenic effects of HAART in type-2 diabetic rats. Methods: Forty-two (42) adult male Sprague-Dawley rats (250 ± 13 g) were divided into non-diabetic and diabetic groups. After induction of diabetes, non-diabetic and diabetic animals were administered either with de-ionized water (DW), HAART (98.2 mg/kg, p.o) or AgNPs +HAART (24.5 mg/kg, i. p) for 8 weeks. Thereafter, metabolic biomarkers, oxidative injury, tissue inflammation, and behavioural changes were evaluated, while the prefrontal cortex was excised for neurochemical analysis. Results: The HAART-treated diabetic rats showed a significant increase in blood glucose level, number of faecal pellets, malondialdehyde (MDA), and pro-inflammatory cytokines (TNF-α, IL-1β) while locomotion, reduced glutathione (GSH), superoxide dismutase (SOD) activity, and PFC-GFAP positive cells were significantly reduced compared with diabetic control. However, administration of AgNPs +HAART to diabetic rats significantly improved the blood glucose level, metabolic activities, SOD, GSH, PFC-GFAP positive cells while reducing MDA and anxiety-like behaviour in the open field test. Conclusion: Administration of HAART aggravates anxiety-like behaviours and promotes neurotoxic effects in the PFC of diabetic rats. However, AgNPs +HAART alleviates the 3 anxiogenic effects of HAART and preserves PFC-GFAP positive cells by reducing oxidative and neuroinflammatory injury.

Background: Although lack of ERβ is an acknowledged risk factor for the development of inflammatory bowel disease (IBD) and psychiatric disorders, the underlying cellular and molecular mechanisms are not fully understood. Here, we revealed the role of gut microbiota in the development of IBD and related anxiety-like behavior in ERβ deficiency mice. Results: In this study, we showed that ERβ knockout mice upon dextran sodium sulfate (DSS) insult displayed significant shifts in fecal microbiota composition with increasing enrichment of genus Prevotellaceae_UCG_001, aggravated colitis severity and anxiety-like behaviors. In addition, DSS induced colitis also enhanced hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in ERβ-deficiency mice, which linked colitis and anxiety-like behaviors. In line with these observations, RNA sequencing data further identified ErbB4 might be the target of ERβ involved in regulating HPA axis hyperactivity caused by DSS insult. Gut microbiota remodeling by co-housing showed both colitis severity and anxiety-like behaviors were aggravated in co-housed WT mice compared with single-housed WT mice, suggesting that gut microbiota plays a critical role in mediating colitis disease activity and related anxiety-like behaviors via aberrant neural processing within the gut-brain axis. Conclusions: Our findings demonstrate ERβ has the potential to inhibit colitis development and anxiety-like behaviors via remodeling of gut microbiota, which reveals ERβ as a promising therapeutic target for treating IBD and related anxiety-like behaviors.

OBJECTIVES: Both prenatal iron deficiency and prenatal alcohol exposure (PAE) decrease body weight, increase susceptibility to anxiety, and impair memory and learning in the offspring. PAE itself causes fetal iron deficiency, even when mothers consume sufficient iron. We hypothesized that iron supplementation in PAE pregnancies would not alter offspring growth but would improve measures of anxiety, learning, and memory. METHODS: Pregnant Long-Evans rats received 5 g/kg/day ethanol or isocaloric maltodextrin (split-dose) from gestational day (GD) 13.5–19.5 and received 6 mg/kg/day iron as ferric sulfate or water from GD12.5–19.5. Male and female offspring were weighed regularly after birth and underwent elevated plus maze (postnatal day (P) 27), open field (P28), novel object recognition (P29–30), T-maze (P32–40), and fear conditioning (P42–50) tests. Mixed model analysis was used to determine significance of the effects of PAE, iron, and sex. RESULTS: PAE reduced postnatal body growth in both male (P = 0.028) and female (P = 0.026) offspring. In both sexes, PAE interacted with age to affect growth (P 0.200). On the novel object recognition test, at delays of both 1 and 24 hours, all groups (except MD + Iron Males with 24-hour delay) recognized the novel object better than chance (P’s 0.120), showing that these did not affect recognition memory. On the T-maze and fear conditioning tests, which assess learning and memory, PAE, iron, and sex had no effect on the results (P’s > 0.080). CONCLUSIONS: This work is the first to investigate gestational iron supplementation as an intervention for alcohol-exposed pregnancies. These results suggest iron supplementation may improve outcomes such as growth in males and anxiety in both sexes in alcohol-exposed populations. FUNDING SOURCES: NIAAA NIDDK.

Zebrafish (Danio rerio) are widely used as a translational model for human neuropsychiatric conditions. Many studies have not considered sex differences in their analyses. Here, we studied sex differences of adult zebrafish in two behavioral domains: Anxiety and Memory. To assess whether sex influences anxiety‐like responses, we used two different behavioral protocols, the novel tank diving task and the light‐dark test. To assess sex differences in learning and memory tasks, we explored two memory domains, short‐term spatial memory (free movement pattern Y‐maze task) and short‐term fear memory (Pavlovian fear conditioning task). Although we did not find any significant difference in learning and memory tasks, female zebrafish showed robust increases in anxiety‐like behavioral endpoints in both anxiety tests. Overall, our data suggest that zebrafish is a sensitive model to work with sex differences when modeling anxiety‐related disorders and this should be an important factor to consider in different experimental designs.

Previously observed antidepressant-like effects of caffeine in adolescent rats have been shown in individually housed (IH) rats. Because IH presents a social stressor that may create depressant-like effects in control animals, this study sought to compare the effects of chronic caffeine in IH and pair-housed (PH) adolescent male and female rats. Housing conditions began on postnatal day 24 (P24) and half of the rats were provided caffeine (0.25 g/l) in their drinking water beginning on P28. Open-field behavior was assessed on P42, a light/dark test was conducted on P43, and a forced swim test was conducted on P44-P45. PH and caffeine separately increased behavior in the open-field test and females reared more than males. In the light/dark test, IH animals and males showed greater anxiety-like behavior than PH animals and females, respectively. In the forced swim test, PH animals showed less overall immobility and caffeine decreased immobility in IH rats and PH females but increased immobility in PH males. Swimming behavior was higher in PH rats overall and caffeine increased swimming in IH rats but decreased swimming in PH rats. Climbing behavior was increased by caffeine in all groups except PH males with the greatest increase in PH females. We conclude that the effects of caffeine on depressive-like and anxiety-like behavior in adolescents are dependent on sex and housing conditions.

N-ethylpentylone (NEP), a new synthetic cathinone, has been rising to be one of the most popular cathinone derivatives in recent years. However, research on NEP is rather limited. In this study, locomotor stimulation and sensitization, as well as anxiety-like behavior induced by NEP were studied in Sprague-Dawley rats, using the open field and elevated plus maze respectively. Rats were administered NEP (5, 20 or 50 mg/kg, intraperitoneal), with saline as the negative control and methamphetamine (5 mg/kg) as a positive control. Acute administration of NEP at all the doses tested significantly promoted locomotor activity, presenting an inverted U-shaped dose-effect curve. The highest activity was observed at the 20 mg/kg dose group, with the average distance traveled 18 times higher than the saline group. Repeated administration of NEP enhanced locomotor activity only at the 5 mg/kg dose group. After a week's withdrawal, re-challenge of NEP failed to induce marked behavioral sensitization. In elevated plus maze experiments, both acute and repeated administration of 20 mg/kg NEP induced anxiolytic-like effects, while no significant alteration was observed in the 5 and 50 mg/kg dose groups. In summary, acute administration of NEP caused significantly enhanced locomotor activity in rats at all the tested doses, while repeated NEP administration enhanced locomotor activity only at a low dose (5 mg/kg), while a high dose (20 mg/kg) of NEP induced anxiolytic-like effects after both acute and repeated administration.

Objectives: The aim of the study was to assess the effect of the extract of Cinnamomum zeylanicum (CZ) bark in the experimental models of pain and anxiety-like behavior in mice. Methods: The extract of CZ bark was administered at the doses of 100, 200, and 400 mg/kg, per orally (p.o) and morphine used as a positive control for pain models, was administered at the dose of 5 mg/kg, intraperitoneally (i.p.). Antinociceptive activity was evaluated using three experimental animal models of pain, namely, tail flick, hot plate, and formalin test. Elevated plus maze test was used to assess the effect on anxiety-like behavior. Rotarod apparatus and actophotometer were used to test muscle coordination and locomotor activity, respectively. Results: Administration of CZ bark extract in the dose of 200 and 400 mg/kg showed significantly increased in the tail-flick latency and latency to reaction time in hot plate test as compared to the control group. In the first phase (0–5 min) of the formalin test, a significant reduction in the pain response was found in CZ (200 and 400 mg/kg) and morphine-treated groups, however during the second phase (30–35 min) significant reduction in formalin-induced pain response was observed in 100, 200, and 400 mg/kg CZ extract-treated group when compared to control group. CZ extract administration at 200 and 400 mg/kg dose caused a significant increase in the percentage of time spent in open arms in the elevated plus maze as compared to the control group. Conclusion: Results suggest that CZ bark extract possesses the antinociceptive activity and modulates anxiety-like behavior.

Background: Alcohol exposure during development has detrimental effects, including a wide range of physical, cognitive and neurobehavioural anomalies known as foetal alcohol spectrum disorders. However, alcohol consumption among pregnant woman is an ongoing latent health problem. Aim: In the present study, the effects of trichostatin A (TSA) on emotional and cognitive impairments caused by prenatal and lactational alcohol exposure were assessed. TSA is an inhibitor of class I and II histone deacetylases enzymes (HDAC), and for that, HDAC4 activity was determined. We also evaluated mechanisms underlying the behavioural effects observed, including the expression of brain-derived neurotrophic factor (BDNF) in discrete brain regions and newly differentiated neurons in the dentate gyrus (DG). Methods: C57BL/6 female pregnant mice were used, with limited access to a 20% v/v alcohol solution as a procedure to model binge alcohol drinking during gestation and lactation. Male offspring were treated with TSA during the postnatal days (PD28-35) and behaviourally evaluated (PD36-55). Results: Early alcohol exposure mice presented increased anxiogenic-like responses and memory deterioration - effects that were partially reversed with TSA. Early alcohol exposure produces a decrease in BDNF levels in the hippocampus (HPC) and prefrontal cortex, a reduction of neurogenesis in the DG and increased activity levels of the HDAC4 in the HPC. Conclusions: Such findings support the participation of HDAC enzymes in cognitive and emotional alterations induced by binge alcohol consumption during gestation and lactation and would indicate potential benefits of HDAC inhibitors for some aspects of foetal alcohol spectrum disorders. The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Ministerio de Economía y Competitividad (Spanish Ministry of Economy and Competitiveness – grant number SAF2016-75966-R-FEDER), and the Spanish Ministry of Health (Retic-ISCIII-RD16/0017/0010 and PNSD 2018/007). SM-R received a postdoctoral fellowship from the Conselleria d’Educació, Investigació, Cultura i Esport (APOSTD/2017/102), Generalitat Valenciana, Spain. LC received an FPI grant (BES-2014-070657) from the Ministerio de Economía y Competitividad, The Department of Experimental and Health Sciences (UPF), ‘Unidad de Excelencia María de Maeztu’ funded by the MINECO (ref. MDM-2014-0370).

A high-fat diet (HFD) and overweight status can induce hippocampal dysfunction, leading to depression and anxiety. Exercise has beneficial effects on emotional behaviors. We previously reported that exercise training rescues HFD-induced excess hippocampal neuronal nitric oxide synthase (nNOS) expression, which is a key regulator of anxiety. Here, we investigated anxiety-like behaviors and hippocampal nNOS expression in response to HFD combined with exercise. Mice were assigned to standard diet, HFD, or HFD with exercise groups for 12 weeks. We found that exercise during the final 6 weeks of the HFD regime improved 12 weeks of HFD-induced defecation, accompanied by rescue of excess nNOS expression. However, anxiety indicators in the elevated plus maze were unchanged. These effects were not apparent after only 1 week of exercise. In conclusion, 6 weeks of exercise training reduced HFD-related anxiety according to one of our measures (defecation), and reversed changes in the hippocampal nNOS/NO pathway.

The extent to which rats express anxiety-like behavior on the elevated plus-maze (EPM) depends on their previous maze experience. Open-arm avoidance develops in maze-experienced rats, and is often accompanied by a diminished anxiolytic response to benzodiazepines. Regions of the dorsal raphe nucleus (DRN) were examined in male Sprague-Dawley rats using c-Fos and serotonin immunohistochemistry following a single exposure, a second exposure or no exposure to the EPM. We then examined the effect of the benzodiazepine anxiolytic chlordiazepoxide (CDP, 5 mg/kg) on EPM behavior and DRN neural activity. Enhanced open-arm avoidance was evident on the second EPM trial in both experiments. The observed pattern of c-Fos expression suggests that the first exposure to the maze activates serotonin cells in the rostral and dorsal regions of the DRN and that only the dorsal subregion is activated by a second exposure. CDP increased open-arm exploration during the first trial, which corresponded to decreased 5-hydroxytryptamine (5-HT) activity in the rostral and ventral subregions of the DRN. However, 5-HT activity in the DRN was reduced in rats on the second maze trial compared with the first trial, when CDP had no effect on open-arm exploration. These results suggest that open-arm avoidance in maze-experienced rats can be characterized as a coping response that is mediated by specific populations of 5-HT neurons in the DRN.

The present study evaluated the effects of blackberry juice that is rich in different concentrations of anthocyanins and polyphenols (2.6 mg/kg anthocyanins, 14.57 mg/kg polyphenols; 5.83 mg/kg ant...

There are many controversies about the safety of extremely low-frequency electromagnetic field (ELF-EMF) on body health and cognitive performance. In the present study, we explored the effects of ELF-EMF on oxidative stress and behaviors of rats. Seventy-two adult male Wistar rats were randomly divided into following groups, control, sham exposure group and the ELF-EMF exposure groups (1 μT, 100 μT, 500 μT, and 2000 μT). After 60 days exposure (2 h/day), elevated plus maze (EPM), Morris water maze (MWM) and Passive avoidance learning (PAL) tasks were used to evaluate the anxiety-like behavior, spatial and passive learning and memory, respectively. Some days after behavioral examination, oxidative stress markers were measured. During spatial reference memory test, animals in ELF-EMF exposure groups (100, and 2000 μT) spent more time in target zone (F (4, 55) = 5.699, P = 0.0007, One-way ANOVA). In PAL retention, the step through latency in the retention test (STLr) in ELF-EMF exposure groups (100,500, and 2000 μT) was significantly greater than control group (F (4, 55) = 29.13, P 0.0001, One-way ANOVA). In EPM test, ELF-EMF exposure (500 and 2000 μT) decreased the percentage of the entries into the open arms (F (4, 55) = 26.31, P 0.0001, one-way ANOVA). ELF-EMF exposure (100, and 500 μT) increased Malondialdehyde (MDA) concentration (F (4, 25) = 79.83, P 0.0001, One-way ANOVA). Our results may allow the conclusion that exposure to ELF-EMFs can improve memory retention (but not acquisition) in the adult male rats. Although exposure to ELF-EMFs could be a factor in the development of anxious state or oxidative stress.

© 2019 The Authors Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).

Graphical abstract, The elevated plus maze is a commonly used and well-validated test of anxiety-related behaviour in rodents. The use of fish in behavioural neuroscience paradigms is increasing, necessitating an equivalent test for studying anxiety-like behaviour in fish. Because behaviour in the elevated plus maze is driven by aversion to open space, the submerged plus maze described here uses transparent walls to elicit similar behaviour in fish. The tendency of fish to explore or avoid the sections of the maze containing transparent walls is used as proxy for anxiety level. This submerged plus maze was designed and validated for convict cichlid (Amatitlania nigrofasciata) fish.

It has been proven that exposure to some drugs even before gestation had transgenerational effects. To investigate the changes which induced by parental morphine exposure before gestation; mainly the anxiety-like behavior, Corticotropin Releasing Factor (CRF) level in the CSF and plasma, CRF Receptor 1 (CRFR1), and the level of protein kinase C (PKC-α) were evaluated in the male offspring. Male and female Wistar rats were exposed to morphine for 21 following days. Ten days after last drug exposure, animals were prepared for mating in 4 distinct groups as follow: drug-naive female and male (used as control), drug-naive female and morphine-abstinent male, drug-naive male and morphine-abstinent female, and morphine abstinent male and female. Offspring were subjected to assess anxiety-like behavior (using elevated plus maze test). CSF and plasma were gathered, and the CRF level was evaluated by ELISA. Using real-time PCR, the CRFR1 level in the brain was evaluated. Results showed that anxiety-like behavior increased in the offspring of morphine-abstinent parent(s) compared with the control group. CRF level in the plasma and CSF also increased in the litter of morphine-abstinent parent(s). CRFR1 mRNA level was upregulated in the brain of offspring with one and/or two morphine-abstinent parent(s). Furthermore, the level of PKC-α was decreased in the brain of offspring which had one and/or two morphine-abstinent parent(s). Taken together, our findings indicated that morphine exposure even before gestation induced transgenerational effects via dysregulation of HPA axis which results in anxiety in the adult male offspring.

Rice beverages are traditionally prepared and consumed popularly by the different ethnic groups of North East India. To investigate its effects on behavior, mice were treated with different fractions of rice beverage that included the beverage as a whole, insoluble and soluble fractions. Intragastric treatments of these fractions were given to the mice (n=6 per group) for 30 days and behavioral studies were performed on elevated plus and Y maze to evaluate anxiety and spatial memory, respectively. Next generation sequencing of metagenomic DNA of the beverage indicated presence of 157 OTUs and 26 bacterial genera were dominant with an abundance of 0.1%. The insoluble fraction treated animals showed lowest anxiety like symptoms. Spatial memory improved in all the treatments compared to the control, of which the rice beverage treatment showed the highest levels (p