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Objetivo: Descrever as características da violência contra adolescentes notificados a partir do Sistema de Vigilância de Violência e Acidentes/VIVA, no Brasil. Material e métodos: Estudo descritivo, com dados do Sistema de Vigilância de Violência e Acidentes/VIVA, Brasil, no período de 2009 a 2016. As variáveis analisadas foram: idade, sexo, raça, local de ocorrência, vinculo do agressor com a vítima e suspeita de uso de álcool nos casos de violência física, psicológica/moral e sexual. Utilizou-se estatística descritiva e o teste de tendência de proporções no STATA. Resultados: A taxa de prevalência da violência física na faixa de 15-19 anos alcançou 104,4 por 100 000 casos, e a prevalência da violência sexual na faixa de 10-14 anos foi de 38,5 por 100 000 casos. A violência sexual alcançou nas meninas a prevalência de 52,0 por 100 000 casos, enquanto que, nos meninos, de 4,5 por 100 000 casos. Houve tendência crescente significativa de violência física na faixa de 15-19, e de violência sexual na faixa de 10-14 anos. Ambos tipos de violência atingiram as raças parda e indígena, acontecendo na residência da vítima, sendo o agressor o namorado. No caso de violência sexual, cresceu a suspeita de uso de álcool pelo agressor. A variação percentual na violência física e psicológica aumentou em mais de 400%. Conclusões: Houve aumento de todos os tipos de violência nestes oito anos. Foram mais frequentes as notificações de violência física e sexual, atingindo principalmente as meninas, na residência, sendo o amigo/conhecido ou namorado da vítima os principais agressores.

Air pollution (AP) triggers neuroinflammation and lipoperoxidation involved in physiopathology of several neurodegenerative diseases. Our study aims to investigate the effect of chronic exposure to ambient AP in oxidative stress (OS) parameters and number of neurons and microglial cells of the cortex and striatum. Seventy-two male Wistar rats were distributed in four groups of exposure: control group (FA), exposed throughout life to filtered air; group PA-FA, pre-natal exposed to polluted air until weaning and then to filtered air; group FA-PA, pre-natal exposed to filtered air until weaning and then to polluted air; and group PA, exposed throughout life to polluted air. After 150 days of exposure, the rats were euthanized for biochemical and histological determinations. The malondialdehyde concentration in the cortex and striatum was significantly higher in the PA group. The activity of superoxide dismutase was significantly decreased in the cortex of all groups exposed to AP while activity of catalase was not modified in the cortex or striatum. The total glutathione concentration was lower in the cortex and higher in the striatum of the FA-PA group. The number of neurons or microglia in the striatum did not differ between FA and PA. On the other hand, neurons and microglia cell numbers were significantly higher in the cortex of the FA-PA group. Our findings suggest that the striatum and cortex have dissimilar thresholds to react to AP exposure and different adaptable responses to chronically AP-induced OS. At least for the cortex, changing to a non-polluted ambient early in life was able to avoid and/or reverse the OS, although some alterations in enzymatic antioxidant system may be permanent. As a result, it is important to clarify the effects of AP in the cortical organization and function because of limited capacity of brain tissue to deal with threatening environments.

Alcohol abuse is one of the main causes of health problems in the world. In response to these alcohol-related health consequences, telehealth supportive counseling has emerged, offering new strategies of dealing with addition problems. Most of telehealth supportive counseling strategies are focused on coping more precisely with positive and negative thinking. The aim of presented study was to examine the relationships between positive thinking, and other coping strategies inherent to human thinking, to refuse alcohol. For this purpose, a total of 232 people participated in the study, all of them were users of a telehealth supportive counseling in Brazil. A batch of questionnaires was employed. This included the sociodemographic information, IDHEA-AD scores and the Coping Behaviours Inventory (CBI-20). After an analysis of mediation, the results indicated that the relationship between negative and positive thinking might be mediated by the assertiveness to refuse. These results suggest that this type of supportive counseling modality might be helpful for users and health professionals. More research is needed to examine the innumerable possibilities of the telehealth tools using as a strategy to deal with the coping variables related to quitting alcohol use.

Chronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This imbalance includes changes in GABA receptors – importantly in GABAA subtypes – and glutamate receptors, especially in NMDA subtypes. A better comprehension of the different roles of GABAAR and NMDAR subunits could be helpful to define new strategies to counteract the deleterious effects observed during alcohol withdrawal. Taurine, a sulfonated amino acid, has been proposed to attenuate alcohol withdrawal symptoms due to its neuromodulatory properties. In this study, we evaluated the correlations between GABAAR and NMDAR subunits in the hippocampus of rats chronically treated with alcohol or in alcohol withdrawal, and the effects of taurine treatment on these parameters. Male Wistar rats received alcohol (2 g/kg) or water by oral gavage (control), 2 × /day, for 28 days. From day 29 to day 33, withdrawal rats received water instead of alcohol and all groups were reallocated to receive 100 mg/kg taurine or saline intraperitoneally (i.p.), once a day. On day 34, rats were euthanized and the hippocampus was dissected for GABAAR α1, α4, δ, and γ2 and NMDAR GluN2A and GluN2B subunits mRNA expression determination by RT qPCR. There were no differences between groups in the studied GABAAR and NMDA subunits. However, we observed a correlation of α1 and γ2 subunits induced by taurine, while in the alcohol group there was a correlation between α4 and GluN2A. In the group treated with alcohol and taurine, we observed an extra correlation, between α1 and GluN2A. After 5 days of withdrawal, a correlation observed in the control group, between δ and GluN2A, was reestablished. The correlation found between subunits suggests a neuroadaptation of GABAergic and glutamatergic systems in withdrawal rats. Results from this study contribute to the elucidation of the mechanisms beyond neuroadaptations observed in alcohol use and withdrawal.

Objectives: Programs for parents have been found to have a direct positive impact on reducing the consumption of psychoactive substances by adolescents, as well as having an indirect impact on reducing risk factors and increasing protective factors. The present study aimed to verify if a telehealth prevention program based on a brief motivational intervention helps to reduce parental risk practices and increase parental protective practices for drug use in comparison with psychoeducation. Methods: A pilot randomized controlled trial was performed at the National Service of Guidance and Information on Drug Use (Ligue 132), from September 2014 to December 2015, with the parents of adolescents (n = 26). The outcome measures were parental style, risk, and protective parental practices. Results: The brief motivational intervention was found to be more effective than psychoeducation in reducing the negligent behavior of parents. Furthermore, when comparing pre- and post-intervention data, the brief motivational intervention helped to change parental style and the large majority of parental practices: increasing positive monitoring, as well as decreasing physical abuse, relaxed discipline, inconsistent punishment, and negative monitoring. Conclusions: These results demonstrate that the telehealth intervention is effective in modifying the parental practices known to help in preventing drug use. Studies with more number of subjects are required so that the results can be substantiated and generalized. Resumo: Objetivos: Os programas para pais parecem ter um impacto positivo direto sobre a redução do consumo de substâncias psicoativas por adolescentes, bem como um impacto indireto sobre a redução dos fatores de risco e aumento dos fatores protetores. O presente estudo visou a verificar se um programa telessaúde de prevenção com base em uma intervenção breve motivacional ajuda a reduzir as práticas de risco dos pais e aumentar as práticas protetoras com relação ao uso de drogas, em comparação à psicoeducação. Métodos: Um ensaio piloto controlado randomizado foi feito no Serviço Nacional de Informações e Orientações sobre Drogas (Ligue 132), de setembro de 2014 a dezembro de 2015, com os pais de adolescentes (n = 26). As medições dos resultados foram o estilo dos pais e as práticas de risco e protetoras dos pais. Resultados: A intervenção breve motivacional parece ser mais eficaz do que a psicoeducação na redução dos comportamentos negligentes dos pais. Adicionalmente, quando comparada aos dados pré e pós-intervenção, a intervenção breve motivacional ajudou a mudar o estilo dos pais e a grande maioria das práticas dos pais: aumentou o monitoramento positivo e reduziu o abuso físico, disciplina permissiva, punição não condizente e monitoramento negativo. Conclusões: Esses resultados demonstram que a intervenção telessaúde é eficaz na mudança das práticas dos pais, conhecida por ajudar a prevenir o uso de drogas. Estudos com maior número de indivíduos são necessários para que os resultados possam ser comprovados e generalizados. Keywords: Prevention, Adolescent, Drug use, Parent programs, Telehealth, Motivational intervention, Palavras-chave: Prevenção, Adolescente, Uso de drogas, Programa para pais, Telessaúde, Intervenção motivacional

The dopaminergic system is associated with cocaine-seeking behaviors, being influenced by other neurotransmitters such as GABA and deregulated by chronic cocaine self-administration. Administration of 6-hydroxydopamine (6-OHDA) to neonatal rats produces a depletion of brain dopamine, mainly, that results in behavioral alterations in adulthood. This model can be applied to better understanding of the role of the dopaminergic system in cocaine use and how its behavioral effects can modulate drug intake. Though there are well-established sex differences in the pattern of drug use, there are no published studies investigating sex-dependent effects of neonatal lesions with 6-OHDA on cocaine self-administration nor regarding GABA

Even though major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are among the most prevalent and incapacitating mental illnesses in the world, their diagnosis still relies solely on the characterization of subjective symptoms (many of which are shared by multiple disorders) self-reported by patients. Thus, the need for objective measures that aid in the detection of and differentiation between psychiatric disorders becomes urgent. In this paper, we explore the potential of neurosteroids and neurotrophic proteins as biomarkers for MDD and PTSD. Circulating levels of the GABAergic neuroactive steroid, allopregnanolone, are diminished in MDD and PTSD patients, which corroborates the finding of depleted neurosteroid levels observed in animal models of these disorders. The neurotrophic protein, brain-derived neurotropic factor (BDNF), is also reduced in the periphery and in the brain of MDD patients and depressed-like animals that express lower neurosteroid levels. Although the role of BDNF in PTSD psychopathology seems less clear and merits more research, we propose a causal link between allopregnanolone levels and BDNF expression that could function as a biomarker axis for the diagnosis of both MDD and PTSD.

The aim of this study was to investigate possible factors that prevent adherence to the treatment of codependent family members of problem drug use individuals. A quasi-experimental study was carried out with 133 relatives of psychoactive substances users who called the Brazilian drug hotline (Ligue 132) between 2013 and 2015, from the five regions of Brazil. The following instruments were used: General service protocol; Family assistance protocol; Holyoake Codependency Index; Behavioral Adherence Scale; and Adherence Factor Questionnaire. Univariate analysis of data was performed for categorical variables and Chi-square test for comparison between variables, with p < 0.05. The sample showed a predominance of women (91.7%), especially mothers (82.7%). Among the investigated factors, alcohol as the substance involved in the problem showed a significant association with the non-adherence to treatment through teleintervention of family members. Resumo O objetivo deste estudo foi investigar possíveis fatores impeditivos da adesão de familiares codependentes a um tratamento. Realizou-se um estudo quase experimental com 133 familiares de usuários de substâncias psicoativas que ligaram para o Ligue 132 no período de 2013 a 2015, sendo que a amostra tem representantes das 5 regiões do Brasil. Os instrumentos utilizados foram: Protocolo geral de atendimento; Protocolo de atendimento ao familiar; Holyoake Codependency Index; Escala de Adesão Comportamental e Questionário de Fatores sobre Adesão. Foram realizadas análises univariadas dos dados para as variáveis categóricas e teste Qui-quadrado para comparação entre as variáveis, p < 0,05. A amostra apresentou o predomínio de mulheres (91,7%) entre os familiares que buscaram ajuda, em especial de mães (82,7%). Dentre os fatores investigados, notou-se que o álcool, entre as substâncias utilizadas pelos usuários, apresentou associação significativa com a não adesão dos familiares a tele intervenção.

Allopregnanolone is a neurosteroid implicated in mood disorders such as depression and anxiety. It acts as a GABAA receptor (GABAAR)-positive allosteric modulator and changes the expression of GABAAR subunits and of brain-derived neurotrophic factor (BDNF) in different brain regions. It has been demonstrated that such neurochemical changes may have an asymmetrical pattern regarding brain hemispheres. The aim of this study was to verify the behavioral and hemisphere-specific neurochemical effects of the bilateral intra-prefrontal cortex (intra-PFC) infusion of allopregnanolone in rats. Rats were exposed to the forced swim test and to the grooming microstructure test, followed by the right and left hemisphere-specific quantification of mRNA expression by Real-Time PCR of δ and γ2 GABAAR subunits and BDNF in the PFC and in the hippocampus. Though we did not observe any significant effects in the behavioral tests, intra-PFC allopregnanolone infusion bilaterally increased the mRNA expression of the δ subunit in the same area and of BDNF in the hippocampus. Both mRNA expressions of the γ2 subunit and BDNF were higher in the right than in the left PFC of control animals, and the hemisphere differences were not seen after allopregnanolone infusion. Overall hippocampal BDNF expression was also higher in the right hemisphere, but this asymmetry was not normalized by allopregnanolone. No asymmetries or changes were observed in the hippocampal mRNA expression of GABAAR subunits. These results point to a hemisphere-dependent regulation of GABAAR subunits and BDNF that can be modulated by intra-PFC allopregnanolone infusion, even in the absence of associated behavioral effects.

Environmental enrichment (EE) has a neuroprotective role and prevents the development of cocaine addiction behavior in rats. Studies showing the role of EE in cocaine toxicity are nonexistent. We hypothesized that rats exposed to EE are protected from cocaine-induced changes in the redox profile and DNA damage after undergoing conditioned place preference (CPP). Ten male Wistar rats were placed in EE cages equipped with toys, a ladder and tunnels, and ten were provided clean, standard laboratory housing (non-EE). EE and non-EE rats were randomly allocated to the classical CPP cocaine vs. saline (COC/Saline) group, where cocaine (15 mg/kg; i.p.) was tested alternately with saline. Afterwards, intracellular reactive species and antioxidant enzymes were evaluated and the comet essay was performed in the prefrontal cortex and hippocampus of rats. As expected, EE rats spent less time in the cocaine-paired chamber, and as a new result, less cocaine-induced DNA damage was observed in the two brain structures. Altogether, our results demonstrate that EE decreases neurotoxicity in brain regions linked to cocaine addiction but does not extinguish it completely.

Cocaine is one of the most popular illicit drug worldwide. Due its great addictive potential, which leads to euphoria and hyperactivity, it is considered a public health concern. At the central nervous system, the drug acts inhibiting catecholamine re-uptake. It is now known that in addition to the toxicity of the drug itself, the contaminants present in the street drug have raised concern about the harmful effects on health. Toxicological in vivo and in vitro studies have demonstrated the toxic effects of cocaine correlated with the generation of reactive oxygen species (ROS), which in turn lead to oxidative damage to the cells. Therefore the aim of this work was to propose an in vitro model that reunites the main parameters of toxicity of the cocaine already observed in the literature so far, and we tested this model using cocaine and seizure cocaine sample (SCS), kindly provided by Federal Police of Brazil. For that, we used a C6 glioblastoma cells and evaluated cell death, oxygen reactive species induction, oxidation of macromolecules as membrane lipids and DNA and loss of mitochondrial membrane potential after cocaine exposure. The results showed that cocaine can decrease cellular viability in a dose-dependent way in the C6 cell immortalized and astrocytes primary culture. Cocaine also induced cellular death by apoptosis. However, in the seizure cocaine sample (SCS), the predominant cell death was due to necrosis. Using dichlorofluorescein (DCF) assay, we confirmed ROS production after cocaine exposition. In agreement with these findings, occurred an increasing in MDA production, as well as increased superoxide dismutase (SOD) and catalase (CAT) activity. The induction of DNA damage was observed after cocaine. Our results demonstrate the occurrence of mitochondrial dysfunction by depolarization of mitochondrial membrane as a consequence of cocaine treatment. In summary, these results demonstrated that cocaine can induce reactive oxygen species formation, leading to oxidative stress. As a consequence of this unbalance, DNA damage, lipidic peroxidation and loss of mitochondrial membrane occurred, which could be an answer to cell death observed.

It is known that among those seeking to cease consumption of alcohol, there can be as high as a 50% relapse rate in the first 12 months. Different tools for treatments have been developed, such as telehealth, with the aim of helping this population. As a result of this demand, technology has gained strength in recent years. A new point of view about the treatment will broaden our knowledge far beyond just efficacy. It seems that understanding the mechanisms that lead to treatment success is as important as knowing its effectiveness. Therefore, the present study examined the relationships between Brief Motivational Intervention by telephone (BMI), motivational stage, outcome, and coping strategies using path analysis. In the post-evaluation, variables such as BMI (randomized individuals), motivational stage and decreased consumption of alcohol reached statistical significance (p

Caffeine and alcohol are some of the most commonly used psychoactive substances in the world, and are often used concomitantly. However, little is known about the effect of caffeine on alcohol consumption. Here, our aim was to investigate the co-exposure of alcohol mixed with caffeine in self-administration. Thirty-two male and thirty-two female Wistar rats were randomly divided into the following groups: control, caffeine (0.25 mg/mL), alcohol (10% v/v) and alcohol mixed with caffeine. After one week of training, the animals underwent self-administration for 21 days (1 h per day) in a fixed ratio of 1 (FR1). The forced swimming test (FST) was performed before the training phase and 24 h after the last self-administration session to verify abstinence-induced depressive-like behaviors. Our results showed that all rats consumed a lower volume of alcohol-containing solution than control solution, and that the presence of caffeine did not influence this parameter. Females consumed less volume of alcohol solution than males but the average dose was similar. Females that self-administered alcohol mixed with caffeine presented a higher immobility in the FST than males that self-administered the same solution. These results support the conclusion that moderate doses of caffeine such as the ones from our study (approximately 7–8 mg/kg/day) do not influence alcohol consumption. Additionally, females might be more susceptible than males to depressive-like effects caused by the abstinence of the use of these substances in combination.

Background: This study aims to identify the association between parenting styles and behavioral changes among adolescents regarding the consumption of alcohol, tobacco, cannabis, cocaine/crack. Methods: A group of ninety-nine adolescents (39 girls and 60 boys), aged 14 to 19 years (17.05 &plusmn, 1.51), who called in to a call center that provides counseling to substance users, was followed-up for 30 days. Data collection occurred between March 2009 and October 2015. The adolescents answered questions regarding parental responsiveness and demanding nature on a scale to assess parental styles and provided sociodemographic data, substance abuse consumption characteristics, and the Contemplation Ladder scale score. Results: The parental styles most reported by the adolescents were authoritative (30%) and indulgent (28%). Children who perceived their mothers as having an indulgent style and who had absent fathers presented more difficulties in making behavioral changes to avoid alcohol and cocaine/crack consumption. Conclusion: The study found that parent-child relationships were associated with a lack of change in the adolescent regarding substance use behavior, particularly the consumption of alcohol and cocaine/crack.

Chronic use of alcohol and its withdrawal impairs the delicate balance between GABAergic and glutamatergic systems. This imbalance includes changes in GABA receptors - importantly in GABA

Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

Animal models show that cocaine sensitization, a behavioral marker of addiction, is more significant in intact gonadal female than male rats and ovariectomy suppress this behavior in female rats. However, few studies explore changes in neurotransmission related to this phenomenon. Here we investigated the in vivo changes on GABA, glutamate, and taurine levels in the medial prefrontal cortex (mPFC) of gonadal intact or ovariectomized female rats after a cocaine challenge administration. Adult female rats were bilaterally ovariectomized (OVX), or sham-operated (SHAM) and randomly assigned to control (CTR), acute (ACT), or repeated (RPT) cocaine administration groups. In the challenge day, after eight days of daily cocaine (15 mg/kg) or saline administration and ten days of washout and stereotaxic surgery, RPT and ACT groups received cocaine, and the CTR group received saline. Horizontal locomotion was monitored concomitantly with microdialysate collection to determine extracellular GABA, glutamate, and taurine levels. Hormonal determination in blood samples confirmed the lower hormonal status of the OVX. Cocaine sensitization occurred in SHAM-RPT female rats after the challenge administration. Non-sensitized OVX-RPT rats showed a peak of GABA at 30 min after cocaine administration, with no change on glutamate and taurine levels. Therefore, elevated GABA levels in the mPFC and lower serum estrogen levels abolish cocaine sensitization behavior in ovariectomized female rats. We discuss some possible implications of these finding for future models of cocaine sensitization research lighting in the female hormonal influence.

Users of cocaine and/or crack may present symptoms of dysphagia due to changes in anatomical structures caused by the use of these substances. The objective of this study was to investigate the presence of symptoms suggestive of dysphagia in users of cocaine and/or crack seeking treatment, as well as to investigate the quality of life of these individuals related to their swallowing condition. A cross-sectional study from September 2015 to December 2016, with 121 users of cocaine and/or crack, was conducted. 59 of them called a telemarketing service and 61 sought treatment at the Centro de Atencao Psicossocial Alcool e Drogas in Porto Alegre (Psychosocial Alcohol and Drug Center). Users were screened and asked to fill the Eating Assessment Tool questionnaire. Users who presented themselves at the center were submitted to the Tool Volume-Viscosity Swallow Test. Users with symptoms of dysphagia responded to the Quality of Life in Swallowing questionnaire. Of all the interviewees, 22.3% (n = 27) reported symptoms suggestive of dysphagia and 2% of the individuals, submitted to swallowing test, presented cough in the liquid consistency. The scores showed a negative impact on quality of life, mainly related to fatigue, sleep, feeding duration, and fear of eating. Significant numbers of users of cocaine and/or crack referred to symptoms suggestive of dysphagia and significant impairments in quality of life, which require specific care in feeding this population in order to assist in their rehabilitation.

Allopregnanolone is a neurosteroid implicated in mood disorders such as depression and anxiety. It acts as a GABA

Substance abuse affects both the user and the family system as a whole, yet substance abuse treatment is centered on the user, leaving the family in the background. Objective: To identify the symptoms of codependency and health issues in the codependent family members of drug users who called a toll-free telephone counseling service. In total, 505 family members participated in this cross-sectional study. Drug users’ mothers and wives who had less than 8 years of education and those who were unemployed had a greater chance of high codependency. It was also determined that a high level of codependency imposed a significant burden on the physical and emotional well-being of those affected, resulting in poor health, reactivity, self-neglect and additional responsibilities. It was concluded that codependency has a negative impact on the family system and on the health of the family members of drug users. Resumo A dependência química atinge o usuário e o sistema familiar como um todo, todavia o tratamento dessa condição é centrado no usuário, o que deixa a família em segundo plano. Objetivo: identificar os sintomas de codependência e questões de saúde em familiares codependentes de usuários de drogas que ligaram para um serviço telefônico de aconselhamento. No total, 505 familiares participaram de um estudo transversal. Mães e esposas de usuários de drogas que tinham menos de 8 anos de estudo e que estavam desempregadas apresentaram maior chance de alta codependência. Além disso, foi identificado que o nível alto de codependência interfere significativamente no bem-estar físico e emocional dos familiares, o que resultou em problemas de saúde, reatividade, autonegligência e sobrecarga de tarefas. Foi concluído que a codependência tem um impacto negativo no sistema familiar e na saúde dos familiares de usuários de drogas.

Alcohol addiction causes severe problems, and its deprivation may potentiate symptoms such as anxiety. Furthermore, ethanol is a neurotoxic agent that induces degeneration and the consequences underlying alcohol-mediated brain damage remain unclear. This study assessed the behavioral changes during acute ethanol withdrawal periods and determined the levels of DNA damage and reactive oxygen species (ROS) in multiple brain areas. Male Wistar rats were subjected to an oral ethanol self-administration procedure with a forced diet where they were offered 8 % (v/v) ethanol solution for 21 days followed by five repeated 24-h cycles alternating between ethanol withdrawal and re-exposure. Control animals received an isocaloric control diet without ethanol. Behavioral changes were analyzed on ethanol withdrawal days in the open-field (OF) and elevated plus-maze (EPM) tests within the first 6 h of ethanol deprivation. The pre-frontal cortex, hypothalamus, striatum, hippocampus, and cerebellum were dissected for alkaline and neutral comet assays and for dichlorofluorescein ROS testing. The repeated intermittent ethanol access enhanced solution intake and alcohol-seeking behavior. Decreased exploratory activity was observed in the OF test, and the animals stretched less in the EPM test. DNA single-strand breaks and ROS production were significantly higher in all structures evaluated in the ethanol-treated rats compared with controls. The animal model of repeated intermittent ethanol access induced behavioral changes in rats, and this ethanol exposure model induced an increase in DNA single-strand breaks and ROS production in all brain areas. Our results suggest that these brain damages may influence future behaviors.

Diabetes mellitus is a metabolic disorder associated with higher risk for depression. Diabetic rats present depressive-like behaviors and taurine, one of the most abundant free amino acids in the brain, reverses this depressive behaviors. Because taurine is a GABA A agonist modulator, we hypothesize that its antidepressant effect results from the interaction on this system by changing α 2 GABA A receptor subunit expression, beside changes on BDNF mRNA, and memory in diabetic rats. Streptozotocin-diabetic and non-diabetic Wistar rats were daily injected with 100 mg/kg of taurine or saline, intraperitoneally, for 30 days. At the end of the experiment, rats were exposed to the novel object recognition memory. Later they were euthanized, the brains were weighed, and the hippocampus was dissected for α 2 GABA A subunit and BDNF mRNA expression. Real-time quantitative PCR (qPCR) showed that diabetic rats presented lower α 2 GABA A subunit and BDNF mRNA expression than non-diabetic rats and taurine increased both parameters in these sick rats. Taurine also reversed the lower brain weight and improved the short-term memory in diabetic rats. Thus, the taurine antidepressant effect may be explained by interference with the GABA system, in line to its neuroprotective effect showed here by preventing brain weight loss and improving memory in diabetic rats.

Depression is a highly incapacitating disorder known to have a multifactorial etiology, including a hereditary genetic background. The neurosteroid allopregnanolone (ALLO) is a positive allosteric modulator of the GABAA receptor and has been shown to have an antidepressant-like effect in animals. This study aimed to assess the behavioral effect of ALLO in animals with different backgrounds of depressive-like activity. An initial population (F0) of male and female Wistar rats was screened for immobility behavior utilizing the Forced Swim Test (FST). Rats with extreme immobility scores were selected for either the High Immobility (HI) group or the Low Immobility (LI) group for breeding, giving origin to the subsequent generations F1 and F2. Guide cannulas were implanted in the lateral ventricle of F2 males for intracerebroventricular infusions of 5 μg/rat of ALLO, 5 μg/rat of imipramine (IMI) or vehicle (CTR), which occurred 24, 5 and 1 h prior to the test session of the drug FST. In the pre-drug FST, a statistically significant difference was observed between the immobility scores from the HI and LI groups of F2 rats. HI rats from F2 also showed significantly higher immobility time when compared to F0. In these HI animals, both IMI and ALLO significantly reduced immobility when compared to the CTR group. IMI-treated rats also showed lower immobility than the ALLO group. In the LI rats, no difference in immobility was found between treatments. In conclusion, two strains of rats with significantly different immobility profiles in the FST were obtained in a relatively short time, after only two generations. Infusions of both ALLO and IMI showed a strain-dependent antidepressant-like effect, being detected in the HI animals but not in the LI animals, which is in line with the clinical understanding that antidepressants have higher efficacy in more severe forms of depression.

We investigated the effect of intermittent hypoxia, mimicking sleep apnea, on axonal integrity, blood-brain barrier permeability, and cognitive function of mice. Forty-seven C57BL mice were exposed to intermittent or sham hypoxia, alternating 30s of progressive hypoxia and 30s of reoxigenation, during 8h/day. The axonal integrity in cerebellum was evaluated by transmission electron microscopy. Short- and long-term memories were assessed by novel object recognition test. The levels of endothelin-1 were measured by ELISA. Blood-brain barrier permeability was quantified by Evans Blue dye. After 14 days, animals exposed to intermittent hypoxia showed hypomyelination in cerebellum white matter and higher serum levels of endothelin-1. The short and long-term memories in novel object recognition test was impaired in the group exposed to intermittent hypoxia as compared to controls. Blood-brain barrier permeability was similar between the groups. These results indicated that hypomyelination and impairment of short- and long-term working memories occurred in C57BL mice after 14 days of intermittent hypoxia mimicking sleep apnea.

Interactions on neurotransmitter systems in the reward pathways may explain the high frequency of combined use of alcohol and cigarettes in humans. In this study, we evaluated some behavioral and neurochemical changes promoted by chronic exposure to alcohol and cigarette smoke in rats. Adult rats were administered with 2 g/kg alcohol (v.o.) or/and inhaled the smoke from 6 cigarettes, twice/day, for 30 days. Behavioral tests were performed 3 h after the alcohol administration and 1 h after the last exposure to cigarette smoke in the morning. Cerebrospinal fluid was collected for glutamate determination and the hippocampus was dissected for GABAA and NMDA receptor subunits mRNA expression determination. Results showed that the combined use of alcohol and cigarette smoke (ALTB) in rats increased the locomotor activity and all interventions decreased anxiety-like behaviors. Despite being on a short-term withdrawal, the cigarette smoke exposure decreased the percentage of open arm entries in the elevated plus maze test, which was prevented by combined use with alcohol. Even though GABAA and glutamate receptor subunits expression did not change in the hippocampus, glutamate levels were significantly higher in the cerebrospinal fluid from ALTB rats. Therefore, we showed that the combined use of alcohol and cigarette maintained a psychostimulant effect after a short-term withdrawal that was associated with the elevated glutamatergic activity. The combined use also prevented anxiety-like signs in cigarette smoke exposure rats, decreasing an adverse effect caused by nicotine withdrawal. These results could explain, in part, the elevated frequency of combined use of these two drugs of abuse in humans.

Bioestatistica, Nucleo de Disciplinas Basicas da Saude, Instituto Metodista IPA, Porto Alegre, Rio Grande do Sul, BrazilThere is increasing evidence suggesting that oxidative stress plays an important role in the development of many chronic and degenerativeconditions such as diabetic encephalopathy and depression. Considering that diabetic rats and mice present higher depressive-like behaviourwhen submitted to the forced swimming test and that treatment with insulin and/or clonazepam is able to reverse the behavioural changes ofthe diabetic rats, the present work investigated the antioxidant status, specifically total antioxidant reactivity and antioxidant potential of in-sulin and clonazepam, as well as the effect of this drugs upon protein oxidative damage and reactive species formation in cortex, hippocam-pus and striatum from diabetic rats submitted to forced swimming test. It was verified that longer immobility time in diabetic rats and insulinplus clonazepam treatment reversed this depressive-like behaviour. Moreover, data obtained in this study allowed to demonstrate throughdifferent parameters such as protein carbonyl content, 2′7′-dichlorofluorescein oxidation, catalase, superoxide dismutase, glutathione perox-idase assay, total radical-trapping antioxidant potential and total antioxidant reactivity that there is oxidative stress in cortex, hippocampusand striatum from diabetic rats under depressive-like behaviour and highlight the insulin and/or clonazepam effect in these different brainareas, restoring antioxidant status and protein damage. Copyright © 2014 John Wiley & Sons, Ltd.key words—diabetes; depression; forced swimming test; GABA agonist; diabetic encephalopathy

Summary We evaluated levels of neuronal DNA damage after acute or repeated cocaine treatment in different brain areas of female rats after ovariectomy or sham surgery. Rats in the control and acute groups were given saline i.p., whereas in the repeated group were given 15 mg/kg, i.p., cocaine for 8 days. After a 10 day washout period, the control group was given saline i.p., whereas rats in the acute and repeated groups were given a challenge dose of 15 mg/kg, i.p., cocaine. After behavioural assessment, rats were killed and the cerebellum, hippocampus, hypothalamus, prefrontal cortex and striatum were dissected for the Comet assay. Acute cocaine exposure induced DNA damage in all brain areas. This effect persisted after repeated administration, except in the hypothalamus, where repeated treatment did not cause increased DNA damage. Sexual hormones exhibited a neuroprotective effect, decreasing cocaine-induced DNA damage in cycling rats in all brain areas.

The original version of this article unfortunately contained a mistake. The spelling of the Sheila Taminini de Almeida name was incorrect.

Quality of life is related to one of the basic human desires, which is to live well and feel good. The scope of this study was to evaluate the quality of life of psychoactive substance users and relatives, compared to non-users, analyzed by socioeconomic strata. A cross-sectional study with users of psychoactive substances, relatives, and other individuals who called the Information and Orientation Service regarding drug abuse. Data collection took place between November 2009 and December 2010. Data was collected from users, relatives, and non-users, including socioeconomic characteristics and data regarding substance consumption when appropriate. In addition to this the abbreviated version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was given to 347 individuals. Among the 138 users (70%) used alcohol, 76 (39%), marijuana, 111 (57%) tobacco, 78 (40%) cocaine and 70 (36%) crack. Control subjects had higher, scores than the relatives of users and users in all areas of the questionnaire (p < 0.05). Psychoactive substance users scored lower in almost all domains and overall score in the WHOQOL-BREF questionnaire in comparison with the sample of non-drug users. These findings reflect poor quality of life of patients and their relatives.

Depression currently affects 350 million people, and its prevalence among adolescents is 4% to 8%. Adolescents who abandon antidepressant treatment or drop out of clinical trials are less likely to recover or experience a remission of symptoms because they are not being followed up by a medical team. The objective of this study was to analyze the dropout rates of randomized clinical trials of depressed adolescents receiving treatment with antidepressant drugs and the factors associated with nonadherence by summarizing this information in a systematic review and meta-analysis.Articles were retrieved from MEDLINE, EMBASE, Cochrane, Clinical Trial, PsycINFO, and Web of Science using the MeSH terms "depressive disorder," "randomized trials," and "adolescents." The evaluation of study quality was performed by using the Cochrane Handbook for Systematic Reviews of Interventions and the Jadad scale.The final sample included 50 articles, of which 44 presented dropout rates. The overall dropout prevalence was 23% (95% CI, 20-27; P0.0001). Participants aged ≥16 years, those treated with serotonin norepinephrine reuptake inhibitors, and those receiving medication only exhibited the highest dropout prevalence, respectively (33% [95% CI, 27-39], 45% [95% CI, 31-64], and 15% [95% CI, 13-17]). The adverse effects most associated with dropout were attempted suicide followed by mania, skin rash, and headache. Problems relating to clinical trials and family arbitration were also related with dropout.Serotonin/norepinephrine reuptake inhibitor treatment, adolescent age16 years, and receiving medication were the only factors demonstrating a higher association with dropout rates. Selective serotonin reuptake inhibitors were linked to the lowest prevalence, probably due to fewer perceived problems with related adverse effects and higher efficacy in adolescents. Cognitive-behavioral therapy combined with pharmacotherapy produced a lower nonadherence prevalence; this approach can be an alternative to avoid dropouts and relapse. Prospero identifier: CRD42014013475.