Effect of taurine on glycaemic, lipid and inflammatory profile in individuals with type 2 diabetes: study protocol of a randomised trial.

Type 2 diabetes mellitus (T2DM) is characterised by chronic hyperglycaemia. Despite the efficacy of conventional pharmacotherapy, some individuals do not reach glycaemic goals and require adjuvant therapies. Taurine, a semi-essential amino acid, decreases blood glucose and cholesterol levels in rodents and humans. However, glycated hemoglobin (HbA1c) has not been evaluated in randomised controlled trials after taurine treatment for more than 12 weeks. This study aims to evaluate the effect of taurine administration on glycaemic, lipid, inflammatory, anthropometric and dietary parameters in individuals with T2DM. A randomised, double-blind, placebo-controlled clinical trial will be conducted at the Clinical Research Center of a tertiary public hospital. Participants with T2DM (n 94) will be recruited and randomised to receive 3 g of taurine or placebo, twice/day, orally, for 12 weeks. Blood samples will be collected before and after 12 weeks of treatment, when HbA1c, fasting glucose, insulin, albuminuria, creatinine, total cholesterol and fractions, triglycerides, C-reactive protein, TNF-α, IL 1, 4, 5, 6, 10 and 13 will be evaluated. Anthropometric parameters and 24-hour food recall will also be evaluated. The study will evaluate the effect of taurine treatment on biochemical and anthropometric parameters in individuals with T2DM. These results will guide the decision-making to indicate taurine treatment as an adjunct in individuals with T2DM who have not reached their glycaemic goal.

Toxic elements in packed red blood cells from smoker donors: a risk for paediatric transfusion?

BACKGROUND AND OBJECTIVES: Smokers currently have no defined restrictions for blood donation. However, cigarette smoke contains toxic substances such as carbon monoxide (CO) and trace elements that can affect the packed red blood cells (PRBCs) quality and safety of transfusion. This study evaluated the effects of smoking on the concentration of essential and trace elements and on carboxyhemoglobin (COHb) levels in PRBCs from smoker donors. MATERIALS AND METHODS: A matched case-control study was conducted to compare COHb levels, determined by the CO-oximetry method, and levels of trace (Cd, Pb, Cr, Ni, As and Hg) and essential (Ca, Mg, Cu, Fe, Mn, Mo, Se and Zn) elements evaluated by inductively coupled plasma mass spectrometry, in PRBCs from smoker (n = 36) and non-smoker (n = 36) donors at Hospital de Clínicas de Porto Alegre, Brazil. RESULTS: Mean COHb level was 14 times higher in the PRBCs obtained from smoker donors (5·9 [4·0-9·1] vs. 0·4 [0·2-0·8]%). Cadmium (1·0 [1·0-1·8] µg/l vs. undetectable) and lead (27 [21-36] vs. 19 [14-26] µg/l) levels were significantly higher in the PRBCs from smokers. Moreover, except for molybdenum, levels of all essential elements were lower in smoker PRBCs. CONCLUSION: The PRBCs donated by smokers contain toxic elements that are probably not safe for transfusion in children. Our results might support changes in the current guidelines of blood banks to improve the transfusion safety through inclusion of inquiry about smoking in the clinical screening, labelling and reserve PRBCs from smoker donors for adults or less critical recipients.

Changes in behavioral and neuronal parameters by alcohol, cigarette, or their combined use in rats.

Few studies have explored the effects of the combined use of alcohol and cigarette in humans, despite its prevalence. Here we evaluated the effect of isolated and combined use on behaviors and neuronal parameters in rats. Male adult rats were divided into alcohol (AL, 2 g/kg, by oral gavage), cigarette smoke (TB, six cigarettes, by inhalation), combined use (ALTB), or control (CT, water by oral gavage and environmental air) groups, treated twice a day (09.00 and 14.00 h). After 4 weeks, the rats were tested in the open field for behavioral analysis and euthanized for brain volume estimation and counting of neurons in the hippocampus. All treatments increased locomotion, and this behavior was higher in the ALTB than TB group. Latency to exit from the central area was lower in the ALTB than in the AL or CT groups. Rearing behavior increased in TB and decreased in AL and ALTB rats. Combined ALTB rats significantly increased their grooming behavior. Only the AL group showed decreased neuron counts and increased brain volume. Our results show that the isolated and combined uses of alcohol and cigarette smoke have diverse effects on behavioral and neuronal parameters in rats after long-term treatment.

Taurine counteracts the neurotoxic effects of streptozotocin-induced diabetes in rats.

Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.

N-acetylcysteine Prevents Alcohol Related Neuroinflammation in Rats.

Alcoholism has been characterized as a systemic pro-inflammatory condition and alcohol withdrawal has been linked to various changes in the brain homeostasis, including oxidative stress and glutamate hyperactivity. N-acetylcysteine (NAC) is an anti-inflammatory and antioxidant multi-target drug with promising results in psychiatry, including drug addiction. We assessed the effects of NAC on the serum and brain inflammatory cytokines after cessation of chronic alcohol treatment in rats. Male Wistar rats received 2 g/kg alcohol or vehicle twice a day by oral gavage for 30 days. Rats were treated, from day 31 to 34, with NAC (60 or 90 mg/kg) or saline, intraperitoneally, once daily. Rats were sacrificed at day 35, trunk blood was collected and the frontal cortex and hippocampus dissected for assessment of TNF-α, IL-1ß, IL-6, IL-18, IL-10. NAC prevented the increase of pro-inflammatory cytokines and the decrease of anti-inflammatory cytokine in the frontal cortex and hippocampus. No changes were observed on serum cytokines. We conclude that NAC protects against inflammation induced by chronic (30 days) alcohol ingestion followed by 5 days cessation in two rat brain areas. Because inflammation has been documented and associated with craving and relapse in alcoholics, the data revealed by this study points to the validity of NAC clinical evaluation in the context of alcohol detoxification and withdrawal.

Effect of Alcohol and Tobacco Smoke on Long-Term Memory and Cell Proliferation in the Hippocampus of Rats.

INTRODUCTION: Alcohol is frequently used in combination with tobacco and few studies explore interactions between these two drugs of abuse. Here, we evaluated the effect of chronic alcohol administration and concomitant exposure to tobacco smoke on long-term memory and on cell proliferation in the hippocampus of rats. METHODS: Forty male Wistar rats were assigned to four groups and treated with alcohol (2g/kg by gavage) and/or exposed to tobacco smoke (from six cigarettes, by inhalation) twice a day (at 9:00 AM and 2:00 PM) for 30 days. Long-term memory was evaluated in the inhibitory avoidance test and hippocampal cell proliferation was analyzed for bromodeoxyuridine immunohistochemistry. RESULTS: Our results showed that alcohol, tobacco smoke, or their combination improved the long-term memory evaluated by the memory index in rats. Moreover, alcohol and tobacco coadministration decreased bromodeoxyuridine-labeled cells by 60% when compared to the control group, while alcohol treatment decreased labeled cells by 40%. The tobacco group showed a nonsignificant 26% decrease in labeled cells compared to the control group. CONCLUSIONS: Chronic alcohol and tobacco coadministration improves the long-term memory in rats in the inhibitory avoidance test. However, coadministration decreases the cell proliferation in the hippocampus of rats, suggesting a deleterious effect by the combined use of these drugs of abuse.

Acute exposure to the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces oxidative stress in different brain area of rats.

The mechanisms that lead to the onset of organoselenium intoxication are still poorly understood. Therefore, in the present study, we investigated the effect of acute administration of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress and on the activity of creatine kinase (CK) in different brain areas and on the behaviour in the open field test of 90-day-old male rats. Animals (n = 10/group) were treated intraperitoneally with a single dose of the organoselenium (125, 250 or 500 µg kg(-1) ), and after 1 h of the drug administration, they were exposed to the open field test, and behaviour parameters were recorded. Immediately after they were euthanized, cerebral cortex, hippocampus and cerebellum were dissected for measurement of thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and CK activity. Our results showed that the dose of 500 µg kg(-1) of the organoselenium increased the locomotion and rearing behaviours in the open field test. Moreover, the organochalcogen enhanced TBARS in the cerebral cortex and cerebellum and increased the oxidation of proteins (carbonyl) only in the cerebral cortex. Sulfhydryl content was reduced in all brain areas, CAT activity enhanced in the hippocampus and reduced in the cerebellum and SOD activity increased in all brain structures. The organoselenium also inhibited CK activity in the cerebral cortex. Therefore, changes in motor behaviour, redox state and energy homeostasis in rats treated acutely with organoselenium support the hypotheses that the brain is a potential target for the organochalcogen action. Ltd.

Asymmetric effects of low doses of progesterone on GABA(A) receptor α4 subunit protein expression in the olfactory bulb of female rats.

The aim of this study was to evaluate the effect of progesterone on the protein expression of α4 subunit of GABA(A) receptor, serotonin transporter (SERT), Akt, Erk, and caspase-3 in the olfactory bulb (OB) of female rats exposed to the forced swimming test (FST). Female rats were injected daily with progesterone (0.4 mg/kg body mass) or vehicle during 2 complete oestrous cycles and exposed to the FST, and the protein expression of GABA(A) receptor α4 subunit, SERT, Akt, Erk, and caspase-3 in the OB were evaluated. Progesterone increased the expression of the α4 subunit in the right OB and decreased its expression in the left OB, although it did not change the expression of other proteins. In summary, our findings indicate that progesterone has an asymmetric modulatory effect on the expression of GABA(A) receptor α4 subunit in the OB. This effect could be related to the antidepressant-like effect of progesterone in female rats.

Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions.

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.

Differential effects of chronic and intermittent administration of taurine on alcohol binge drinking in male rats.

Episodic consumption of high doses of alcohol in a short period (binge drinking - BD) among adolescents is known to be harmful to their brain development. Chronic use of taurine increases voluntary alcohol consumption and shows an anxiolytic-like effect in rats. In this study, we evaluated the differential effects of chronic and intermittent taurine administration on alcohol consumption and behavioral changes in adolescent and young adult rats subjected to the BD model. Male Wistar rats (35 days old) were divided into 4 groups for daily intraperitoneal administration of saline (SAL); taurine, 100mg/kg (TAU); taurine on BD days and saline on intervals (TAU/SAL); and saline on BD days and taurine on intervals (SAL/TAU). They were exposed to 4 cycles of BD, with free access to alcoholic solution (20% w/v), for 2h, 3 days per week. At the end of the 3rd cycle, anxiety-like behaviors were assessed using the light-dark task. After euthanasia, plasma and prefrontal cortex samples were collected to measure corticosterone and BDNF levels, respectively. Chronic taurine treatment did not alter alcohol consumption in rats, whereas intermittent administration increased alcohol intake after 4 BD exposures (TAU/SAL: +19.4% and SAL/TAU: +21.6%). No anxiolytic-like effects were found by taurine administration, nor were there changes in serum corticosterone or BDNF levels in the frontal cortex of young adult rats. Intermittent taurine, but not chronic treatment, increased alcohol intake among rats after the second week of exposure. The translation of these results to humans is concerning since the combination of alcohol and drinks containing taurine is common among adolescent and young adult individuals.

Evaluation of behavioral and neurochemical changes induced by carbofuran in zebrafish (Danio rerio).

Carbofuran (CF) is a carbamate class pesticide, widely used in agriculture for pest control in crops. This pesticide has high toxicity in non-target organisms, and its presence in the environment poses a threat to the ecosystem. Research has revealed that this pesticide acts as an inhibitor of acetylcholinesterase (AChE), inducing an accumulation of acetylcholine in the brain. Nonetheless, our understanding of CF impact on the central nervous system remains elusive. Therefore, this study explored how CF influences behavioral and neurochemical outcomes in adult zebrafish. The animals underwent a 96-hour exposure protocol to different concentrations of CF (5, 50, and 500 µg/L) and were subjected to the novel tank (NTT) and social preference tests (SPT). Subsequently, they were euthanized, and their brains were extracted to evaluate neurochemical markers associated with oxidative stress and AChE levels. In the NTT and SPT, CF did not alter the evaluated behavioral parameters. Furthermore, CF did not affect the levels of AChE, non-protein sulfhydryl groups, and thiobarbituric acid reactive species in the zebrafish brain. Nevertheless, further investigation is required to explore the effects of environmental exposure to this compound on non-target organisms.

Alcohol, place conditioning, and male rats: A systematic review of outcome prediction.

Although Place Conditioning (PC) has been used to study the motivational effects of alcohol for almost 50 years, variables and situations in which alcohol induces PC in rats are still unclear, especially for short PC protocols (up to 10 conditioning trials). The aim of this systematic review was to predict primary outcomes (namely, conditioning failure, conditioned place aversion (CPA), and conditioned place preference (CPP)) of alcohol-induced PC with male outbred rats. We sought relevant records in PUBMED and two other sources. Two reviewers independently assessed records for eligible articles (those meeting all inclusion criteria), selected alcohol-induced PC experiments (those meeting no exclusion criteria) from eligible articles, extracted data, and assessed the quality of included studies. We then conducted a predictive analysis of outcomes by examining procedure-outcome relations according to variables known to affect associative learning, alcohol interventions in rats, and PC interventions themselves. We selected 192 experiments (133 short protocols, 27 long protocols, and 32 protocols with alcohol pre-exposure) from 62 articles to compose the review. Rates of conditioning failure are mainly predicted by interactions of alcohol dose and the number of habituation sessions and conditioning trials. Different conditions (housing systems) and characteristics (age and weight) of animals predict CPA and CPP: higher rates of CPA are predicted by single-housed, older, and heavier animals, while higher rates of CPP are predicted by group-housed, younger, and lighter animals. We recommend settings for CPP induction in short protocols, discuss the broad theoretical and translational consequences of the predictive analysis for the use of PC in alcohol research, and specify variables needing more careful investigation. This review could improve our understanding of the results of alcohol-induced PC with rats, refine our understanding of the motivational function of alcohol and alcohol-seeking behavior triggered by environmental contexts, and open new avenues of research on their neurobiological basis.

Antidepressant effect of taurine in diabetic rats.

Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

Effect of chronic administration of the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on oxidative stress in different brain areas of rats.

Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions. Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received the vinyl chalcogenide (125, 250 or 500 µg/kg body weight) intraperitoneally once a day during 30 days. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen action.

Acute administration of the organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces biochemical and hematological disorders in male rats.

Organochalcogens are extensively produced and employed by industry and agriculture, and the risk of occupational and environmental toxicity to them has been poorly understood. Here, we investigated the acute effect of a new organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on biochemical and hematological parameters in male Wistar rats. The animals were treated with a single intraperitoneal injection of the organochalcogen at doses of 125, 250 or 500 µg·kg(-1). After 60 min, the animals were sacrificed by decapitation, and the trunk blood was collected for determination of glucose, triglycerides, cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase, lactate dehydrogenase, urea, creatinine, C-reactive protein, red blood cells, hematocrit, hemoglobin and white blood cells (WBC). Our results showed a reduction in cholesterol levels in all treated groups, an increase in ALT activity at doses of 250 and 500 µg·kg(-1), a decrease of hemoglobin and an increase in WBC in animals that received 250 and 500 µg·kg(-1) of the organoselenium. In addition, we observed an increase in neutrophil counts at 125 µg·kg(-1) dose and a decrease at 500 µg·kg(-1) dose. We also verified an increase in lymphocyte counts at the dose of 500 µg·kg(-1). Thus, the present study shows that the acute treatment with this new organochalcogen causes biochemical changes and hematological disorders in male rats.

Effect of progesterone on the expression of GABA(A) receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere.

Progesterone is a neuroactive hormone with non-genomic effects on GABA(A) receptors (GABA(A)R). Changes in the expression of GABA(A)R subunits are related to depressive-like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABA(A)R α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats (n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg⁻¹) or vehicle, during two complete female estrous cycles (8-10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive-like behaviors and GABA(A)R α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABA(A)R γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABA(A) system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABA(A) R α1 subunit expression in the right prefrontal cortex of female rats.

Social distancing and changes in drug use: Results from a cross-sectional study during the COVID-19 pandemic in Brazil.

Background: The outbreak of coronavirus disease 19 has led to measures of social distancing and quarantine worldwide. This stressful period may lead to psychological problems, including changes in substance use. In addition, sociodemographic factors are linked to changed levels of drug use and abuse observed during the COVID-19 pandemic, which are also associated with increased anxiety, depression, and other disorders. Thus, the aim of the study was to investigate (i) changes in drug use during the COVID-19 pandemic associated with social distancing, and (ii) to verify factors associated with those changes. Methods: A web-based cross-sectional observational survey was completed by a self-selected adult general population in Brazil (N = 2,435) during September/October 2020 (first wave) before and throughout the pandemic. Key outcomes: social distancing, self-reported drug use (ASSIST), and emotional states (DASS-21). Results: High social distancing was associated with fewer chances (prevalence ratio) of increased drug use for alcohol (0.71, CI95%: 0.64-0.80), tobacco (0.72; CI95%: 0.60-0.87), cannabis (0.65; CI95%: 0.55-0.78), and others. Low social distancing presented a higher DASS-21 score for anxiety (P = 0.017). Concerning covariates analysis by a general linear model, men (alcohol: 1. 71; cannabis: 3.86), younger age (alcohol: 0.97), less education (alcohol, tobacco, cannabis and cocaine/crack comparing several lower schooling categories vs. higher education), lower income (alcohol: 0.42; tobacco: 0.47; and cannabis: 0.36), and higher depression DASS-21 score (alcohol: 1.05; tobacco: 1.08; cannabis: 1.07; and cocaine/crack: 1.07) were associated with higher use prevalence of several drugs. Conclusions: Individuals reporting low social distancing increased the use of most drugs during the pandemic, while high social distancing significantly decreased drug use. Anxiety and depressive states and several sociodemographic factors (men; lower income; less education) were associated with higher drug use patterns.

Low-cost apparatus for cigarette smoke exposure in rats.

BACKGROUND: The effects of tobacco smoke on the central nervous system are usually studied with isolated nicotine, ignoring other compounds present in cigarette smoke. The few studies that use in vivo whole-body cigarette smoke exposure are usually performed in expensive commercial apparatus. NEW METHOD: We presented a feasible, safe, and low-cost apparatus for cigarette smoke exposure in rodents. RESULTS: Rats exposed to cigarette smoke in this apparatus showed cotinine levels similar to human active smokers. Additional results showed that cigarette smoke exposure increased glutamate and aspartic acid levels and decreased leucine, isoleucine, ornithine, phenylalanine, and tryptophan levels in the cerebrospinal fluid of rats. COMPARISON WITH EXISTING METHOD(S): Our apparatus is feasible, safe, and costs 67-fold less than a commercial automatized smoking machine. Beyond the low cost, it does not require specialized knowledge for building or maintenance. CONCLUSIONS: We concluded that our low-cost apparatus is reliable and reproduces cigarette smoke use in humans.

The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS.

The NMDA receptor antagonist ketamine can induce a rapid improvement in depressive symptoms that often endures for days after a single intravenous dose. The pharmacodynamic basis for this effect is poorly understood. Using a proton magnetic resonance spectroscopy ([(1)H]-MRS) method that previously detected a normalization of amino acid neurotransmitter (AANt) content after chronic treatment with conventional antidepressant treatments, we examined whether the acute action of ketamine is associated with alterations in AANt content as well. Ten subjects with major depressive disorder (MDD) received saline, then ketamine in a fixed order, one week apart, under single-blind conditions. Each infusion was associated with three [(1)H] MRS scans (baseline, 3h and 48 h post-infusion) that measured glutamate, GABA and glutamine within the occipital cortex. Rating scales were administered before, during and after each infusion. The rapid (1h) and sustained (at least 7 days) antidepressant effect we observed after ketamine infusion was not associated with either baseline measures of, or changes in, occipital AANt content. Dissociative symptoms were not correlated with changes in depression scores. While our results indicate that changes in occipital AANt content are not a correlate of ketamine's antidepressant action, this may only apply to the regional and temporal windows of our MRS measurements.

Anti-stress effects of the glucagon-like peptide-1 receptor agonist liraglutide in zebrafish.

Stress-related disorders are extremely harmful and cause significant impacts on the individual and society. Despite the limited evidence regarding glucagon-like peptide-1 receptor (GLP-1R) and mental disorders, a few clinical and preclinical studies suggest that modulating this system could improve symptoms of stress-related disorders. This study aimed to investigate the effects of liraglutide, a GLP-1R agonist, on neurobehavioral phenotypes and brain oxidative status in adult zebrafish. Acute liraglutide promoted anxiolytic-like effects in the light/dark test, while chronic treatment blocked the impact of unpredictable chronic stress on behavioral and physiological parameters. Taken together, our study demonstrates that liraglutide is active on the zebrafish brain and may counteract some of the effects induced by stress. More studies are warranted to further elucidate the potential of GLP-1R agonists for the management of brain disorders.