Prevalence and factors associated with depression and anxiety among medical students in an inland university in Brazil / Prevalência e fatores associados à depressão e ansiedade entre estudantes de medicina de uma universidade do interior do Brasil

Medical schools are known to be stressful environments for students, and hence medical students have been believed to experience greater incidences of depression and anxiety than the general population or students from other spe-cialties. The present study investigates the prevalence of anxiety and depressive symptoms together with factors as-sociated with them among medical students in a federal public university in the south of Brazil. A descriptive study was performed using self-administered questionnaires to access socio-demographic, institutional, and health variables in association with two scales - Beck's Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI) - designed to assess depressive and anxiety symptoms, respectively. The research sample consisted of 152 subjects. The depres-sive symptoms prevalence was 65.1% (BDI > 9), state-anxiety was 98.6%, and trait-anxiety was 97.4% (STAI > 33). Among women, 37.8% demonstrated moderate/severe depressive symptoms. High levels of state-anxiety symptoms and trait-anxiety symptoms were found in 44.7% of students under the age of 20. In the group with the lowest month-ly income, it was observed the highest distributions for moderate/severe depressive symptoms, high state and high trait-anxiety symptoms, corresponding to 47.4%, 57.9%, and 47.4%, respectively. Students attending the third term of medical school had the highest percentage of moderate/severe depressive symptoms (62.5%) and high state-anxiety symptoms (50%). In addition, students who had both financial aid programs presented the highest percentages of moderate/severe depressive symptoms (46.2%), highstate-anxiety symptoms (61.5%), and high trait-anxiety symptoms (46.2%). We also observed a correlationbetween depression and trait-anxiety symptoms (P = 0.037). In conclusion, it was identified as risk factors for depressive symptoms the previous depression diagnosis, previous search for health service due to psychological symptoms, being in financial aid programs, dissatisfaction with the medical school, and inadequate psychological help offered by it. For state-anxiety symptoms and trait-anxiety outcome, there is an increased risk among low-income or students who have financial help from financial aid programs and younger age students. (AU)

Objetivo: Investigar a prevalência de sintomas de ansiedade e depressão e fatores associados a eles entre es-tudantes de medicina de uma universidade pública do sul do Brasil. Métodos: Foi realizado um estudo descritivo através de questionários autoaplicáveis para avaliar variáveis sociodemográficas, institucionais e de saúde, associa-das a duas escalas - Inventário de Depressão de Beck (BDI) e Inventário de Traço-Estado de Ansiedade (STAI) - para avaliar os sintomas de depressão e ansiedade, respectivamente. Resultados: A prevalência de sintomas depres-sivos foi de 65,1% (BDI > 9), estado de ansiedade foi de 98,6% e traço de ansiedade de 97,4% (STAI > 33). Uma correlação significativa foi encontrada entre depressão e traço de ansiedade. Diagnóstico prévio de depressão, busca prévia por serviços de saúde, insatisfação com o curso de medicina e ter auxílio de baixa renda e bolsa de iniciação científica foram identificados como fatores de risco para depressão. Estudantes com baixa renda mensal e menores de 25 anos apresentaram maior risco para estado de ansiedade. Idade, ano da faculdade de medicina e programa de ajuda financeira provaram ser um fator de risco para traço de ansiedade. Conclusão: Esses resultados mostram fatores significativos relacionados à saúde mental de estudantes de uma faculdade de medicina recém-fundada no interior do Brasil. (AU)

Cannabidiol treatment prevents drug reinstatement and the molecular alterations evoked by amphetamine on receptors and enzymes from dopaminergic and endocannabinoid systems in rats.

In psychostimulant drug addiction, relapse is the most concerning outcome to be managed, considering there is no approved treatment for this neuropsychiatric condition. Here, we investigated the effects of the CBD treatment on the relapse behavior triggered by stress, after being submitted to the amphetamine (AMPH)-induced conditioned place preference (CPP) in rats. To elucidate the mechanisms of action underlying the CBD treatment, we evaluated the neuroadaptations on dopaminergic and endocannabinoid targets in the ventral striatum (VS) and ventral tegmental area (VTA) of the brain. Animals received d,l-AMPH (4 mg/kg, i.p.) or vehicle in the CPP paradigm for 8 days. Following the first CPP test, animals were treated with CBD (10 mg/kg, i.p.) or its vehicle for 5 days and subsequently submitted to forced swim stress protocol to induce AMPH-CPP relapse. Behavioral findings showed that CBD treatment prevented AMPH-reinstatement, also exerting anxiolytic activity. At the molecular level, in the VTA, CBD restored the CB1R levels decreased by AMPH-exposure, increased NAPE-PLD, and decreased FAAH levels. In the VS, the increase of D1R and D2R, as well as the decrease of DAT levels induced by AMPH were restored by CBD treatment. The current outcomes evidence a substantial preventive action of the CBD on the AMPH-reinstatement evoked by stress, also involving neuroadaptations in both dopaminergic and endocannabinoid systems in brain areas closely involved in the addiction. Although further studies are needed, these findings support the therapeutic potential of CBD in AMPH-relapse prevention.

Cannabidiol prevents amphetamine relapse and modulates D1- and D2-receptor levels in mesocorticolimbic brain areas of rats.

Amphetamine (AMPH) is an addictive psychostimulant highly used worldwide and its consumption is related to neurotoxic effects. Currently, there is no pharmacotherapy approved for treating AMPH or other psychostimulant drug addiction. Different studies have shown promising properties of cannabidiol (CBD) for treating many neurological and psychiatric diseases, and recently, CBD is being considered a potential strategy for the treatment of drug addiction disorders. Thus, we investigated possible CBD beneficial effects on relapse symptoms following AMPH re-exposure considering drug relapse is the most difficult clinical factor to control during addiction treatment. Rats received d,l-AMPH (4 mg/kg, i.p.) or vehicle in the conditioned place preference (CPP) paradigm (8 days), when each experimental group was re-assigned to receive CBD at two different doses (5 or 10 mg/kg, i.p) or control, for 5 days. Subsequently, animals were re-exposed to AMPH-CPP (4 mg/kg, i.p.) for 3 additional days to assess relapse behavior. Besides locomotor and anxiety-like behaviors, dopaminergic molecular parameters were quantified in both prefrontal cortex and ventral striatum. Regarding molecular levels, CBD modulated at basal levels the dopaminergic targets (D1R, D2R, DAT, and TH) in the assessed brain areas, preventing AMPH relapse and decreasing anxiety-like behavior per se and in AMPH-CPP animals. The current findings give evidence about CBD-induced AMPH-relapse prevention, which may be linked to dopaminergic mesocorticolimbic system modulation. Although future and clinical studies are needed, our outcomes show that CBD may be a useful alternative to prevent AMPH relapse.

Trans fat intake during pregnancy or lactation increases anxiety-like behavior and alters proinflammatory cytokines and glucocorticoid receptor levels in the hippocampus of adult offspring.

Changes in dietary habits, including the increased consumption of processed foods, rich in trans fatty acids (TFA), have profound effects on offspring health in later life. Thus, this study aimed to assess the influence of maternal trans fat intake during pregnancy or lactation on anxiety behavior, as well as markers of inflammation, oxidative stress, and expression of glucocorticoid receptors (GR) of adult male offspring. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0 g/kg body weight) during pregnancy or lactation. After weaning, male offspring received only standard diet. On the postnatal day 60, anxiety-like symptoms were assessed, the plasma was collected for the quantification of cytokines levels and the hippocampus removed for biochemical and molecular analysis. Our findings have evidenced that offspring from HVF-supplemented dams during pregnancy or lactation showed significantly greater levels of anxiety behavior. HVF supplementation increased plasma levels of proinflammatory cytokines and these levels were higher in the lactation period. In contrast, HVF supplementation decreased plasma levels of IL-10 in relation to SO/FO in both periods. Biochemical evaluations showed higher reactive species generation, protein carbonyl levels and catalase activity in offspring from HVF-supplemented dams during lactation. In addition, offspring from HVF-supplemented dams showed decreased GR expression in both supplemented periods. Together, these data indicate that consumption of TFA in different periods of development may increase anxiety-like behavior at least in part via alterations in proinflammatory and anti-inflammatory cytokine levels and GR expression in limbic brain regions.

Omega-3 decreases D1 and D2 receptors expression in the prefrontal cortex and prevents amphetamine-induced conditioned place preference in rats.

Amphetamine (AMPH) abuse is a serious public health problem due to the high addictive potential of this drug, whose use is related to severe brain neurotoxicity and memory impairments. So far, therapies for psychostimulant addiction have had limited efficacy. Omega-3 polyunsaturated fatty acids (n-3 PUFA) have shown beneficial influences on the prevention and treatment of several diseases that affect the central nervous system. Here, we assessed the influence of fish oil (FO), which is rich in n-3 PUFA, on withdrawal and relapse symptoms following re-exposure to AMPH. Male Wistar rats received d,l-AMPH or vehicle in the conditioned place preference (CPP) paradigm for 14 days. Then, half of each experimental group was treated with FO (3 g/kg, p.o.) for 14 days. Subsequently, animals were re-exposed to AMPH-CPP for three additional days, in order to assess relapse behavior. Our findings have evidenced that FO prevented relapse induced by AMPH reconditioning. While FO prevented AMPH-induced oxidative damages in the prefrontal cortex, molecular assays allowed us to observe that it was also able to modulate dopaminergic cascade markers (DAT, TH, VMAT-2, D1R and D2R) in the same brain area, thus preventing AMPH-induced molecular changes. To the most of our knowledge, this is the first study to show a natural alternative tool which is able to prevent psychostimulant relapse following drug withdrawal. This non-invasive and healthy nutraceutical may be considered as an adjuvant treatment in detoxification clinics.

Effects of Fish and Grape Seed Oils as Core of Haloperidol-Loaded Nanocapsules on Oral Dyskinesia in Rats.

Haloperidol is a widely used antipsychotic, despite the severe motor side effects associated with its chronic use. This study was carried out to compare oral dyskinesia induced by different formulations of haloperidol-loaded nanocapsules containing caprylic/capric triglycerides, fish oil or grape seed oil (GSO) as core, as well as free haloperidol. Haloperidol-loaded lipid-core nanocapsules formulations were prepared, physicochemical characterized and administered (0.5 mg kg-1-ip) to rats for 28 days. Oral dyskinesia was evaluated acutely and subchronically and after that cell viability and free radical generation in cortex and substantia nigra. All formulations presented satisfactory physicochemical parameters. Acutely, all formulations were able to prevent oral dyskinesia development in comparison to free haloperidol, except haloperidol-loaded nanocapsules containing GSO, whose effect was only partial. After subchronic treatment, all haloperidol-loaded nanocapsules formulations prevented oral dyskinesia in relation to free drug. Also, haloperidol-loaded nanocapsules containing fish oil and GSO were more effective than caprylic/capric triglycerides nanocapsules and free haloperidol in cell viability preservation and control of free radical generation. Our findings showed that fish oil formulation may be considered as the best formulation of haloperidol-loaded lipid-core nanocapsules, being able to prevent motor side effects associated with chronic use of antipsychotic drugs, as haloperidol.

Maternal trans fat intake during pregnancy or lactation impairs memory and alters BDNF and TrkB levels in the hippocampus of adult offspring exposed to chronic mild stress.

This study aimed to assess the influence of maternal dietary fat intake during pregnancy or lactation on memory of adult offspring after chronic mild stress (CMS) exposure. Female Wistar rats were supplemented daily with soybean oil/fish oil (SO/FO) or hydrogenated vegetable fat (HVF) by oral gavage (3.0g/kg body weight) during pregnancy or lactation. On post-natal day (PND) 60, half of the animals were exposed to CMS following behavioral assessments. While the adult offspring born under influence of SO/FO and HVF supplementations during pregnancy showed higher levels of n-3 and n-6 fatty acids (FA) series DHA and ARA metabolites, respectively, in the hippocampus, adult offspring born from supplemented dams during lactation showed higher levels of their precursors: ALA and LA. However, only HVF supplementation allowed TFA incorporation of adult offspring, and levels were higher in lactation period. Adult offspring born from dams supplemented with trans fat in both pregnancy and lactation showed short and long-term memory impairments before and after CMS. Furthermore, our study also showed higher memory impairment in offspring born from HVF-supplemented dams during lactation in comparison to pregnancy. BDNF expression was increased by stress exposure in offspring from both SO/FO- and HVF-supplemented dams during pregnancy. In addition, offspring from HVF-supplemented dams showed decreased TrkB expression in both supplemented periods, regardless of stress exposure. In conclusion, these findings show for the first time that the type of dietary FA as well as the period of brain development is able to change FA incorporation in brain neural membranes.

Trans fat intake across gestation and lactation increases morphine preference in females but not in male rats: Behavioral and biochemical parameters.

The abuse of morphine has risen considerably in recent years, mainly due to the increase of its prescription in clinical medicine. Also, increased consumption of processed foods, rich in trans fatty acids (TFA), has caused concerns about human health. Thus, the aim of our study was to determine whether trans fat consumption in the perinatal period may affect preference for morphine in adolescent female and male rats. Dams were orally supplemented with water (C-control) or hydrogenated vegetable fat (HVF-rich in TFA) during gestation and lactation periods. On post-natal day 43, pups were exposed to morphine (4mg/kg i.p., for 4 days) and assessed in the conditioned place preference paradigm. Anxiety-like symptoms were assessed, and oxidative status of the brain was estimated by reactive species (RS) generation. Female rats with HVF supplementation showed increased morphine preference and less anxiety-like symptoms. Additionally, both male and female rats from HVF-supplementation showed increased RS generation in the ventral tegmental area, whose level was similar in morphine-conditioned female rats. RS generation was increased in the hippocampus of morphine-conditioned female rats, regardless of the supplementation of their dams. We may infer that gender is a predictive factor to opioid preference, since adolescent female rats showed more susceptibility to addiction than males. Furthermore, trans fat consumption across the perinatal period is able to modify parameters of opioid preference in female rats, possibly due to TFA incorporation in phospholipid membranes, modifying the endogenous opioid system and the oxidative status in brain areas related to drug addiction.

Antioxidant protection of gallic acid against toxicity induced by Pb in blood, liver and kidney of rats.

The effect of the antioxidant gallic acid (GA) on Pb toxicity in blood, liver and kidney was investigated in the present study. Rats Wistar received Pb nitrate (50 mg/Kg/day, i.p., 5 days) followed by GA (13.5 mg/Kg, p.o., 3 days) or a chelating agent (EDTA, 55 mg/Kg, i.p.). As result, Pb decreased body weight, hematocrit and blood δ-aminolevulinic acid dehydratase (ALA-D) activity. In addition, high Pb levels were observed in blood and tissues, together with increased (1) lipid peroxidation in erythrocytes, plasma and tissues, (2) protein oxidation in tissues and (3) plasma aspartate transaminase (AST) levels. These changes were accompanied by decreasing in antioxidant defenses, like superoxide dismutase (SOD) activity in tissues and catalase (CAT) activity and reduced glutathione (GSH) in liver. GA was able to reverse Pb-induced decrease in body weight and ALA-D activity, as well as Pb-induced oxidative damages and most antioxidant alterations, however it did not decrease Pb bioaccumulation herein as EDTA did. Furthermore, EDTA did not show antioxidant protection in Pb-treated animals as GA did. In conclusion, GA decreased Pb-induced oxidative damages not by decreasing Pb bioaccumulation, but by improving antioxidant defenses, thus GA may be promising in the treatment of Pb intoxications.

Cross-Generational trans Fat Consumption Favors Self-Administration of Amphetamine and Changes Molecular Expressions of BDNF, DAT, and D1/D2 Receptors in the Cortex and Hippocampus of Rats.

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids--TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

Olive oil-enriched diet reduces brain oxidative damages and ameliorates neurotrophic factor gene expression in different life stages of rats.

Our aim was to assess the influence of maternal diet rich in monounsaturated fatty acids on oxidative and molecular parameters in brains of mouse pups as well as their body weight during their lifetime. Female rats received a diet containing 20% of olive oil-enriched diet (OOED) and a standard diet control diet (CD) in different periods: pregnancy, lactation and after weaning until pups' adulthood. On the last prenatal day (Group 1), embryos from OOED group showed smaller body weight, brain weight and lower levels of sulphydryl groups glutathione reduced (GSH) in the brain. On postnatal delay-21 (PND21) (Group 2), pups from OOED group showed higher body weight and brain weight, reduced brain weight/body weight ratio and lower brain lipid peroxidation (LP). On PND70 (Group 3), pups from OOED group showed lower brain LP and higher levels of GSH in prefrontal cortex and lower brain levels of reactive species in the hippocampus. Interestingly, the group of animals whose diet was modified from OOED to CD on PND21 showed greater weight gain compared to the group that remained in the same original diet (OOED) until adulthood. Furthermore, OOED consumption during pregnancy and lactation significantly increased BDNF only, as well as its main transcripts exon IV and VI mRNA levels in the prefrontal cortex. In addition, OOED significantly up-regulated FGF-2 mRNA levels in the prefrontal cortex. These findings open a pioneering line of investigation about dietary adjunctive therapeutic strategies and the potential of healthy dietary habits to prevent neonatal conditions and their influence on adulthood.

Toxicological aspects of trans fat consumption over two sequential generations of rats: Oxidative damage and preference for amphetamine.

Chronic consumption of processed food causes structural changes in membrane phospholipids, affecting brain neurotransmission. Here we evaluated noxious influences of dietary fats over two generations of rats on amphetamine (AMPH)-conditioned place preference (CPP). Female rats received soybean oil (SO, rich in n-6 fatty acids (FA)), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans fatty acids (TFA)) for two successive generations. Male pups from the 2nd generation were maintained on the same supplementation until 41 days of age, when they were conditioned with AMPH in CPP. While the FO group showed higher incorporation of n-3 polyunsaturated-FA (PUFA) in cortex/hippocampus, the HVF group showed TFA incorporation in these same brain areas. The SO and HVF groups showed AMPH-preference and anxiety-like symptoms during abstinence. Higher levels of protein carbonyl (PC) and lower levels of non-protein thiols (NPSH) were observed in cortex/hippocampus of the HVF group, indicating antioxidant defense system impairment. In contrast, the FO group showed no drug-preference and lower PC levels in cortex. Cortical PC was positively correlated with n-6/n-3 PUFA ratio, locomotion and anxiety-like behavior, and hippocampal PC was positively correlated with AMPH-preference, reinforcing connections between oxidative damage and AMPH-induced preference/abstinence behaviors. As brain incorporation of trans and n-6 PUFA modifies its physiological functions, it may facilitate drug addiction.

Prolonged consumption of trans fat favors the development of orofacial dyskinesia and anxiety-like symptoms in older rats.

Polyunsaturated fatty acids (FAs) are cell membrane components involved in brain functions. We hypothesized that long-term trans fat consumption is able to modify the membrane FAs composition impairing behavioral parameters related to aging. In this study, a comparison of behavioral parameters at 10 and 15 months of trans fat consumption by male Wistar rats was made. Animals were fed for 10 and 15 months from weaning with diets containing either 20% w/w soybean oil (SO), rich in n-6 PUFA, hydrogenated vegetable fat (HVF), rich in trans FAs, or a standard diet (control - C). At both evaluation times, HVF-fed rats showed progressively increased parameters of orofacial dyskinesia, fear and anxiety-like symptoms. The HVF diet reduced locomotor and exploratory activities progressively over 10 and 15 months of supplementation, while the standard and SO diets did not. In this study, we showed that chronic trans FAs consumption from weaning is able to favor the development of neuromotor and neuropsychiatric diseases, whose intensity was time dependent.

Hepatoprotective effects of pecan nut shells on ethanol-induced liver damage.

The hepatoprotective activity of the aqueous extract of the shells of pecan nut was investigated against ethanol-induced liver damage. This by-product of the food industry is popularly used to treat toxicological diseases. We evaluated the phytochemical properties of pecan shell aqueous extract (AE) and its in vitro and ex vivo antioxidant activity. The AE was found to have a high content of total polyphenols (192.4±1.9 mg GAE/g), condensed tannins (58.4±2.2 mg CE/g), and antioxidant capacity, and it inhibited Fe(2+)-induced lipid peroxidation (LP) in vitro. Rats chronically treated with ethanol (Et) had increased plasmatic transaminases (ALT, AST) and gamma glutamyl transpeptidase (GGT) levels (96%, 59.13% and 465.9%, respectively), which were effectively prevented (87; 41 and 383%) by the extract (1:40, w/v). In liver, ethanol consumption increased the LP (121%) and decreased such antioxidant defenses as glutathione (GSH) (33%) and superoxide dismutase (SOD) (47%) levels, causing genotoxicity in erythrocytes. Treatment with pecan shell AE prevented the development of LP (43%), GSH and SOD depletion (33% and 109%, respectively) and ethanol-induced erythrocyte genotoxicity. Catalase activity in the liver was unchanged by ethanol but was increased by the extract (47% and 73% in AE and AE+Et, respectively). Therefore, pecan shells may be an economic agent to treat liver diseases related to ethanol consumption.

Haloperidol-loaded polysorbate-coated polymeric nanocapsules decrease its adverse motor side effects and oxidative stress markers in rats.

Haloperidol is the most widely used antipsychotic drug in the treatment of psychiatric disorders. Despite its satisfactory therapeutic effect, its chronic use is related to severe motor side effects. Here, we investigate the incidence of motor side effects of haloperidol-loaded nanocapsules when compared to free haloperidol and the relation with oxidative stress (OS) development. Both vehicle (B-NcFO) and haloperidol loaded polysorbate-coated nanocapsules suspension (H-NcFO) prepared with fish oil as core showed uniform and rounded particles, nanometric size, negative zeta potential, low polydispersity indices and high encapsulation efficiency. Wistar rats received a single dose of free haloperidol (FH), B-NcFO or H-NcFO (0.2 mg/kg ip) and were submitted to acute motor side effects evaluation 1 h after the injection. Lower catalepsy time and oral dyskinesia were observed in H-NcFO-treated group than in FH group; however, both formulations decreased animals' locomotor activity. In a experiment performed subchronically, rats injected daily with H-NcFO (0.2 mg/kg-ip) for 28 days showed decreased oral dyskinesia frequency and catalepsy time and no impairment on locomotor activity as compared to FH group (0.2 mg/kg-ip). FH group showed higher OS, as observed by increased lipid peroxidation and reduced glutathione levels and catalase activity in extrapyramidal region. Our findings showed that nanocapsules may be an efficient form to prevent or minimize haloperidol motor side effects, which are related to OS development, ameliorating psychiatric patients' quality of life.

Locomotor damage and brain oxidative stress induced by lead exposure are attenuated by gallic acid treatment.

We investigated the antioxidant potential of gallic acid (GA), a natural compound found in vegetal sources, on the motor and oxidative damages induced by lead. Rats exposed to lead (50 mg/kg, i.p., once a day, 5 days) were treated with GA (13.5mg/kg, p.o.) or EDTA (110 mg/kg, i.p.) daily, for 3 days. Lead exposure decreased the locomotor and exploratory activities, reduced blood ALA-D activity, and increased brain catalase (CAT) activity without altering other antioxidant defenses. Brain oxidative stress (OS) estimated by lipid peroxidation (TBARS) and protein carbonyl were increased by lead. GA reversed the motor behavior parameters, the ALA-D activity, as well as the markers of OS changed by lead exposure. CAT activity remained high, possibly as a compensatory mechanism to eliminate hydroperoxides during lead poisoning. EDTA, a conventional chelating agent, was not beneficial on the lead-induced motor behavior and oxidative damages. Both GA (less) and EDTA (more) reduced the lead accumulation in brain tissue. Negative correlations were observed between the behavioral parameters and lipid peroxidation and the lead levels in brain tissue. In conclusion, GA may be an adjuvant in lead exposure, mainly by its antioxidant properties against the motor and oxidative damages resulting from such poisoning.