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We investigated the effect of a chronic palatable diet rich in simple sugars on memory of different degrees of emotionality in male adult rats, and on hippocampal plasticity markers in different stages of development. On postnatal day (PND) 21, 45 male Wistar rats were divided in two groups, according to their diet: (1-Control) receiving standard lab chow or (2-Palatable Diet) receiving both standard chow plus palatable diet ad libitum. At PND 60, behavioral tests were performed to investigate memory in distinct tasks. Hippocampal plasticity markers were investigated at PND 28 in half of the animals, and after the behavioral tests. Palatable diet consumption induced an impairment in memory, aversive or not, and increased Na+ , K+ -ATPase activity, both at PND 28, and in the adulthood. Synaptophysin, brain-derived neurotrophic factor (BDNF), and protein kinase B (AKT), and phosphorylated AKT were reduced in the hippocampus at PND 28. However, at PND 75, this diet consumption led to increased hippocampal levels of synaptophysin, spinophilin/neurabin-II, and decreased BDNF and neuronal nitric oxide synthase. These results showed a strongly association of simple sugars-rich diet consumption during the development with memory impairments. Plasticity markers are changed, with results that depend on the stage of development evaluated.
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Variations in serotoninergic signaling have been related to behavioral outcomes. Alterations in the genome, such as DNA methylation and histone modifications, are affected by serotonin neurotransmission. The amygdala is an important brain region involved in emotional responses and impulsivity, which receives serotoninergic input. In addition, studies suggest that the serotonin transporter gene network may interact with the environment and influence the risk for psychiatric disorders. We propose to investigate whether/how interactions between the exposure to early life adversity and serotonin transporter gene network in the amygdala associate with behavioral disorders. We constructed a co-expression-based polygenic risk score (ePRS) reflecting variations in the function of the serotonin transporter gene network in the amygdala and investigated its interaction with postnatal adversity on attention problems in two independent cohorts from Canada and Singapore. We also described how interactions between ePRS-5-HTT and postnatal adversity exposure predict brain gray matter density and variation in DNA methylation across the genome. We observed that the expression-based polygenic risk score, reflecting the function of the amygdala 5-HTT gene network, interacts with postnatal adversity, to predict attention and hyperactivity problems across both cohorts. Also, both postnatal adversity score and amygdala ePRS-5-HTT score, as well as their interaction, were observed to be associated with variation in DNA methylation across the genome. Variations in gray matter density in brain regions linked to attentional processes were also correlated to our ePRS score. These results confirm that the amygdala 5-HTT gene network is strongly associated with ADHD-related behaviors, brain cortical density, and epigenetic changes in the context of adversity in young children.
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During development, the brain goes through fundamental processes, including organization of neural networks and plasticity. Environmental interventions may change initial brain programming, leading to long-lasting effects and altering the susceptibility to psychopathologies, including depression disorder. It is known that depression is a psychiatric disorder with a high prevalence worldwide, including high rates among adolescents. In this study, we evaluated whether social isolation in the prepubertal period and chronic use of high-fat diet (HFD) may induce depressive-like behavior in male adult rats. We also investigated hippocampal plasticity markers and neurotransmitter systems. We found both social isolation and HFD induced a depressive-like behavior in the forced swimming task. Moreover, chronic HFD reduced synaptic markers in hippocampus, demonstrated by reductions in ßIII-tubulin (neuronal marker), PSD-95, SNAP-25, and neurotrophin-3. The HFD group also presented decreased glutamatergic and GABAergic receptors subunits. On the other hand, stress affected hippocampal brain-derived neurotrophic factor (BDNF) signaling pathways, and increased expression of subunit of the NMDA receptor (NR2A). Both factors (stress and diet) decreased GR in the hippocampus without affecting plasma corticosterone at basal levels. Interactions between early stress and HFD access were observed only in the BNDF receptor (tropomyosin receptor kinase B; TrkB) and synaptophysin. In summary, these findings showed that a brief social isolation and chronic HFD, during a sensitive developmental period, cause depressive-like behavior in adulthood. The mechanisms underlying these behavioral effects may involve changes in the levels of synaptic proteins in hippocampus: HFD consumption appears to affect synaptic markers, while social isolation affected BDNF signaling more significantly.
Assuntos
Comportamento Animal , Depressão/etiologia , Depressão/fisiopatologia , Hipocampo/fisiopatologia , Plasticidade Neuronal , Estresse Psicológico/complicações , Animais , Biomarcadores/metabolismo , Depressão/psicologia , Dieta Hiperlipídica , Ácido Glutâmico/metabolismo , Hipocampo/patologia , Masculino , Modelos Biológicos , Ratos Wistar , Receptores de Glucocorticoides/metabolismo , Maturidade Sexual , Isolamento Social/psicologia , Sacarose , Ácido gama-Aminobutírico/metabolismoRESUMO
Neonatal handling has an impact on adult behavior of experimental animals and is associated with rapid and increased palatable food ingestion, impaired behavioral flexibility, and fearless behavior to novel environments. These symptoms are characteristic features of impulsive trait, being controlled by the medial prefrontal cortex (mPFC). Impulsive behavior is a key component of many psychiatric disorders such as attention deficit hyperactivity disorder (ADHD), manic behavior, and schizophrenia. Others have reported a methylphenidate (MPH)-induced enhancement of mPFC functioning and improvements in behavioral core symptoms of ADHD patients. The aims of the present study were: (i) to find in vivo evidence for an association between neonatal handling and the development of impulsive behavior in adult Wistar rats and (ii) to test whether neonatal handling could have an impact on monoamine levels in the mPFC and the pharmacological response to MPH in vivo. Therefore, experimental animals (litters) were classified as: "non-handled" and "handled" (10[Formula: see text]min/day, postnatal days 1-10). After puberty, they were exposed to either a larger and delayed or smaller and immediate reward (tolerance to delay of reward task). Acute MPH (3[Formula: see text]mg/Kg. i.p.) was used to suppress and/or regulate impulsive behavior. Our results show that only neonatally handled male adult Wistar rats exhibit impulsive behavior with no significant differences in monoamine levels in the medial prefrontal cortex, together with a decreased response to MPH. On this basis, we postulate that early life interventions may have long-term effects on inhibitory control mechanisms and affect the later response to pharmacological agents during adulthood.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Manobra Psicológica , Comportamento Impulsivo/efeitos dos fármacos , Comportamento Impulsivo/fisiologia , Metilfenidato/farmacologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Monoaminas Biogênicas/metabolismo , Peso Corporal/efeitos dos fármacos , Condicionamento Operante , Modelos Animais de Doenças , Feminino , Masculino , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Gravidez , Ratos , Ratos Wistar , Reforço Psicológico , Fatores Sexuais , Fatores de TempoRESUMO
Pre-puberty is a critical period for the final maturation of the neural circuits that control energy homeostasis, as external stimuli such as exposure to diets and stress may influence the adaptive responses with long-term repercussions. Our aim is to investigate the effects of isolation stress during early life and of chronic access to palatable diets, rich in sugar or fat, on the metabolic profile (glycemia, plasma lipids, leptin and cholinesterase activity) and oxidative stress parameters in the livers of adult male rats. We observed changes mainly in animals that received the high-fat diet (increased body weight and abdominal fat in adults, as well as increased plasma glucose, and cholinesterase activity), and most of these effects were further increased by exposure to stress. High-fat diet also affected the rats' lipid profile (increased cholesterol, LDL-cholesterol and triglycerides); these effects were more marked in stressed animals. Additionally, exposure to stress led to an oxidative imbalance in the liver, by increasing production of reactive species, as well as the activity of antioxidant enzymes (superoxide dismutase and catalase); these effects were accentuated with the high-fat diet (which also caused a severe reduction in glutathione peroxidase activity). Taken together, these results show that the pre-pubertal period constitutes a critical window for stressful interventions during development, leading to alterations in metabolic parameters and increased oxidative stress during adulthood that may be more pronounced in animals that receive a high-fat diet.
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Gordura Abdominal/crescimento & desenvolvimento , Glândulas Suprarrenais/crescimento & desenvolvimento , Envelhecimento/metabolismo , Lipídeos/sangue , Fígado/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Isolamento Social , Gordura Abdominal/efeitos dos fármacos , Gordura Abdominal/metabolismo , Envelhecimento/efeitos dos fármacos , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Colinesterases/sangue , Gorduras na Dieta/farmacologia , Sacarose Alimentar/farmacologia , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Energia/efeitos dos fármacos , Radicais Livres/metabolismo , Glutationa Peroxidase/metabolismo , Leptina/sangue , Fígado/efeitos dos fármacos , Masculino , Tamanho do Órgão , Ratos , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Social isolation during early development is one of the most potent stressors that can cause alterations in the processes of brain maturation, leading to behavioral and neurochemical changes that may persist to adulthood. Exposure to palatable diets during development can also affect neural circuits with long-term consequences. The aims of the present study were to investigate the long-term effects of isolation stress during the pre-pubertal period on the exploratory and anxiety-like behavior, the oxidative stress parameters and the respiratory chain enzymes activities in the hippocampus of adult male rats under chronic palatable diets. The results showed that isolated rats receiving either normal or high-fat diet during the pre-pubertal period presented an anxiolytic-like behavior. The animals exposed to stress and treated with high-carbohydrate diet, rich in disaccharides, on the other hand, presented the opposite pattern of behavior. Stress in the pre-pubertal period also leads to decreased activity of the antioxidant enzymes and the mitochondrial respiratory chain complexes II and IV and decreased total thiol content. These effects were reversed by high-fat diet when it was associated with stress. The effects of a sub-acute pre-pubertal isolation stress on anxiety-like behavior and on hippocampal oxidative imbalance during adulthood appear to be modulated by different types of diets, and probably different mechanisms are involved.
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Ansiedade , Comportamento Animal , Dieta , Estresse Oxidativo , Maturidade Sexual , Animais , Transporte de Elétrons , Masculino , Ratos , Isolamento SocialRESUMO
Tamoxifen (TAM) is a selective estrogen receptor modulator (SERM) used in the treatment of breast cancer; however many women complain of weight gain during TAM treatment. The anorectic effects of estradiol (E) and TAM are well known, although the effects of E on the consumption of palatable food are controversial and there is no information regarding the effects of TAM on palatable food consumption. The aim of this study was to investigate the effects of chronic treatment with estradiol and/or tamoxifen on feeding behavior in ovariectomized rats exposed to standard chow and palatable foods (Froot Loops® or chocolate). Additionally, parameters such as body weight, uterine weight, lipid profile and plasma glucose were also measured. Wistar rats were ovariectomized (OVX) and subsequently injected (ip.) for 40 days with: E, TAM, E+TAM or vehicle (OVX and SHAM - controls). Behavioral tests were initiated 25 days after the start of treatment. Froot Loops® consumption was evaluated in a novel environment for 3 min. Standard chow intake was evaluated for two days and chocolate intake for 7 days in the home cage in a free choice model (chocolate or standard chow). Rats injected with E, TAM and E+TAM groups showed a reduction in body weight and standard chow intake, compared with control groups. With regard to palatable food intake, the E, TAM and E+TAM groups demonstrated increased consumption of Froot Loops®, compared with the SHAM and OVX groups. In contrast, all groups increased their consumption of chocolate, compared with standard chow; however the E group consumed more chocolate than the OVX, TAM and E+TAM groups. Despite these differences in chocolate consumption, all groups showed the same caloric intake during the chocolate exposure period; however the TAM and E+TAM groups presented decreased body weight. Treatment with estradiol and tamoxifen showed a favorable lipid profile with low levels of TC, LDL, LDL/HDL ratio and lower levels of plasma glucose. The E group presented high levels of TG and HDL, when compared with the TAM and E+TAM groups. Taken together, results suggest that TAM acted in an estrogen-like manner on the majority of parameters analyzed. However, tamoxifen acts in a different manner depending on the type of palatable food and the exposure. In addition, the TAM group demonstrated weight loss, compared with other groups independently of the type of food presented (palatable food or standard chow), showing a low caloric efficiency.
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Glicemia/metabolismo , Estradiol/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Lipídeos/sangue , Tamoxifeno/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Estradiol/administração & dosagem , Feminino , Ovariectomia , Ratos , Moduladores Seletivos de Receptor Estrogênico/farmacologia , Tamoxifeno/administração & dosagem , Útero/efeitos dos fármacosRESUMO
OBJECTIVES: Social isolation during the prepubertal period may have long-term effects on metabolism. The exposure to stressful events is associated with increased palatable food intake, constituting reward-based eating. However, palatable food consumption in early life may lead to metabolic alterations later in life. We investigated whether isolation stress during early life can lead to metabolic alterations in male and female rats with or without exposure to a palatable diet. METHODS: Animals were stressed by isolation during one week after weaning, with or without exposure to a palatable diet. RESULTS: Stress and palatable diet induced increased caloric consumption. In females, there was a potentiation of consumption in animals exposed to stress and palatable diet, reflected by increased weight gain and triacylglycerol levels in juveniles, as well as increased adiponectin levels. Most of the effects had disappeared in the adults. Different effects were observed in males: in juveniles, stress increased unacylated ghrelin levels, and hypothalamic neuropeptide Y (NPY). Subsequently, adult males that were exposed to a palatable diet during prepuberty showed increased body weight and retroperitoneal fat deposition, increased glycemia, and decreased plasma adiponectin and hypothalamic NPY. Exposure to stress during prepuberty led to increased adrenals during adulthood, decreased LDL-cholesterol and increased triacylglycerol levels. CONCLUSION: Isolation stress and consumption of palatable diet changes metabolism in a sex-specific manner. Prepuberty female rats were more prone to stress effects on food consumption, while males showed more long-lasting effects, being more susceptible to a metabolic programming after the consumption of a palatable diet.
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Ingestão de Alimentos , Maturidade Sexual/fisiologia , Isolamento Social , Estresse Psicológico/metabolismo , Adiponectina/sangue , Animais , Glicemia/análise , Feminino , Hipotálamo/química , Insulina/sangue , Masculino , Neuropeptídeo Y/análise , Ratos , Ratos Wistar , Caracteres Sexuais , Aumento de PesoRESUMO
The exposure to adverse events early in life may affect brain development. Omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the development of mood and anxiety disorders. The aim of this study was to examine the interaction between variations in the early environment (handling or maternal separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on locomotor activity, sucrose preference, forced swimming test and on serum and hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups. Pups were removed from their dams (incubator at 32°C on postnatal days (PND) 1-10) during 10 min/day (H) or 3h/day (MS). On PND 35, males were subdivided into diets adequate or deficient in n-3 PUFA for 15 weeks. H and MS gained weight differently, and animals receiving the n-3 PUFA deficient diet gained less weight. MS displayed a higher food consumption and higher consumption of sucrose solution during the second hour of exposure to the sucrose preference test. No differences were observed in the swimming test. H group had increased locomotion and showed a higher response to amfepramone. No significant effect was observed on serum BDNF levels. BDNF protein levels were decreased in animals receiving the n-3 PUFA deficient diet. We observed that early life environment and a mild n-3 PUFA deficiency are able to affect several behavioral aspects (food and sucrose consumption and locomotor response), and lead to a differential hippocampal BDNF metabolism in adult life.
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Ácidos Graxos Ômega-3/farmacologia , Privação Materna , Estresse Psicológico/metabolismo , Animais , Animais Recém-Nascidos , Peso Corporal , Fator Neurotrófico Derivado do Encéfalo/sangue , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Dieta com Restrição de Gorduras/efeitos adversos , Dietilpropiona/farmacologia , Ácidos Graxos Ômega-3/metabolismo , Feminino , Preferências Alimentares , Manobra Psicológica , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Resposta de Imobilidade Tônica , Masculino , Atividade Motora/efeitos dos fármacos , Gravidez , Ratos , Estresse Psicológico/sangue , Estresse Psicológico/dietoterapia , Estresse Psicológico/psicologiaRESUMO
The effects of neonatal handling and the absence of ovarian hormones on the olfactory memory related to a palatable food in adulthood were investigated. Oxidative stress parameters and Na+/K+-ATPase activity in the hippocampus and olfactory bulb of adult pre-puberty ovariectomized female rats handled or not in the neonatal period were also evaluated. Litters were non-handled or handled (10 min/day, days 1-10 after birth). Females from each litter were divided into: OVX (subjected to ovariectomy), sham, and intact. When adults, olfactory memory related to a palatable food (chocolate) was evaluate using the hole-board olfactory task. Additionally, oxidative stress parameters and Na+/K+-ATPase activity were measured in the hippocampus and olfactory bulb. No difference between groups was observed considering olfactory memory evaluation. Neonatal handled rats presented an increase in Na+/K+-ATPase activity in the hippocampus and in the olfactory bulb, compared to non-handled ones. Considering the surgical procedure, there was a decrease in Na+/K+-ATPase and catalase activities in sham and OVX groups, compared to intact animals in the olfactory bulb. We concluded that olfactory memory related to a palatable food in adulthood was not affected by neonatal handling or by pre-puberty surgery, with or without removal of ovaries. The difference observed between groups in catalase and Na+/K+-ATPase activity does not seem to be related to the olfactory memory. Additionally, the increase in Na+/K+-ATPase activity (an enzyme that maintains the neurochemical gradient necessary for neuronal excitability) induced by neonatal handling may be related to neuroplastic changes in the hippocampus and olfactory bulb.
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Manobra Psicológica , Hipocampo/metabolismo , Memória/fisiologia , Bulbo Olfatório/metabolismo , Percepção Olfatória/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Ração Animal , Animais , Catalase/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Ovariectomia , Estresse Oxidativo/fisiologia , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , PaladarRESUMO
Early life events can change biochemical, endocrine and behavioral aspects throughout the life of an animal. Since there is a strong relationship between stress, neonatal handling and feeding behavior, the aim of this study was to investigate the effects of these three factors on behavioral parameters (anxiety and locomotion), oxidative stress in brain structures (prefrontal cortex and hippocampus) and on plasma glucose. Nests of Wistar rats were handled (10 min/day), or not (control groups), on days 1-10 after birth. Males from these groups were divided into 4 subgroups: (1) stressed by isolation in childhood (pre-puberty) and with access to a highly palatable diet (2) stressed by isolation and receiving standard lab chow (3) not isolated and receiving a highly palatable diet and (4) not isolated and receiving standard chow. The animals were kept under these conditions for 7 days. Rats receiving the highly palatable diet consumed more food, more calories, gained more weight and had a higher plasma glucose level, but had a lower caloric efficiency than the standard chow groups. Both handling and palatable diet were able to increase food consumption on the first day of isolation. Isolation stress had an anxiogenic effect in the plus maze, which was counteracted by handling. Palatable diet increased time spent in the central area of the open field apparatus and in the open arms of the elevated plus maze, showing an anxiolytic effect. The use of both these conditions, however, does not appear to bring additional protection against the effects of stress during this particular period of life, i.e., pre-puberty. In the prefrontal cortex, handling reduced thiol content and appears to imbalance the antioxidant enzymes system, which is counteracted by a palatable diet. Hippocampus seems to be more sensitive than the prefrontal cortex to early interventions, especially to the highly palatable diet, and both handling and diet appear to imbalance the antioxidant enzyme system. Thus, measurements of antioxidant enzymes activities indicate that handling may endanger some brain structures and that the palatable diet was able to prevent some handling effects on antioxidant enzymes, depending on the brain structure.
Assuntos
Ansiedade/psicologia , Dieta , Estresse Oxidativo/fisiologia , Glândulas Suprarrenais/fisiologia , Animais , Glicemia/metabolismo , Peso Corporal/fisiologia , Catalase/metabolismo , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Feminino , Glutationa Peroxidase/metabolismo , Manobra Psicológica , Hipocampo/metabolismo , Masculino , Atividade Motora/fisiologia , Tamanho do Órgão/fisiologia , Córtex Pré-Frontal/metabolismo , Gravidez , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismoRESUMO
Early life experiences have profound influences on behavior and neurochemical parameters in adult life. The aim of this study is to verify neonatal handling-induced sex specific differences on learning and reversal learning as well as oxidative stress parameters in the prefrontal cortex and striatum of adult rats. Litters of rats were non-handled or handled (10 min/day, days 1-10 after birth). In adulthood, learning and reversal learning were evaluated using a Y maze associated with palatable food in male and female rats. Morris water maze reversal learning was verified in males. Oxidative stress parameters were evaluated in both genders. Male neonatal handled animals had a worse performance in the Y maze reversal learning compared to non-handled ones and no difference was observed in the water maze reversal learning task. Regarding females, neonatal handled rats had a better performance during the Y maze learning phase compared to non-handled ones. In addition, neonatal handled female animals showed a decreased SOD/CAT ratio in the PFC compared to non-handled females. We conclude that neonatal handling effects on learning and memory in adult rats are sex and task specific. The sex specific differences are also observed in the evaluation of antioxidant enzymes activities with neonatal handling affecting only females.
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Antioxidantes/metabolismo , Regulação Enzimológica da Expressão Gênica/fisiologia , Manobra Psicológica , Reversão de Aprendizagem/fisiologia , Caracteres Sexuais , Animais , Animais Recém-Nascidos , Catalase/metabolismo , Comportamento de Escolha , Corpo Estriado/enzimologia , Corpo Estriado/crescimento & desenvolvimento , Feminino , Masculino , Aprendizagem em Labirinto/fisiologia , Córtex Pré-Frontal/enzimologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Gravidez , Ratos , Ratos Wistar , Tempo de Reação , Espécies Reativas de Oxigênio/metabolismo , Compostos de Sulfidrila/metabolismo , Superóxido Dismutase/metabolismo , Fatores de TempoRESUMO
Early life events lead to behavioral and neurochemical changes in adulthood. The aim of this study is to verify the effects of neonatal handling on spatial memory, nitric oxide (NO) production, antioxidant enzymatic activities and DNA breaks in the hippocampus of male and female adult rats. Litters of rats were non-handled or handled (10 min/day, days 1-10 after birth). In adulthood they were subjected to a Morris water maze or used for biochemical evaluations. Female handled rats showed impairment in spatial learning. They also showed decreased NO production, while no effects were observed in these parameters in male rats. No effects were observed on the number of hippocampal NADPH diaphorase positive cells. In the Comet Assay, male handled rats showed increased DNA breaks index when compared to non-handled ones. We conclude that neonatal handling impairs learning performance in a sex-specific manner, what may be related to NO decreased levels.
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Quebras de DNA , Manobra Psicológica , Hipocampo/metabolismo , Memória , Óxido Nítrico/biossíntese , Percepção Espacial , Animais , Catalase/metabolismo , Ensaio Cometa , Feminino , Glutationa Peroxidase/metabolismo , Masculino , Aprendizagem em Labirinto , NADPH Desidrogenase/metabolismo , Ratos , Ratos Wistar , Fatores Sexuais , Superóxido Dismutase/metabolismoRESUMO
Caffeine is widely consumed in beverages and food, and its consumption in high doses is associated with anxiety increase. Stress situations are often associated to coffee consumption, and have a strong influence on oxidative DNA damage. As there are sex-specific differences in many metabolic, neurochemical and behavioral aspects, the aim of this study is to verify the interaction between chronic consumption of caffeine and chronic stress on anxiety and DNA breaks in the hippocampus on male and female rats. Wistar rats were submitted to restraint stress for at least 50 days. The diet consisted of standard rat chow and caffeine 0.3 or 1 g/L in drinking water "ad libitum" as the only drinking source. Controls received tap water. Anxiety-like behavior and DNA breaks in the hippocampus were evaluated. Caffeine consumption and chronic stress increased anxiety-like behavior as well as DNA breaks in the hippocampus of male rats. No effect on these parameters was observed in females. These results may be related to the presence of estradiol, which may have anxiolytic and neuroprotective properties.
Assuntos
Ansiedade/fisiopatologia , Cafeína/administração & dosagem , Estimulantes do Sistema Nervoso Central/administração & dosagem , Quebras de DNA , Hipocampo/química , Estresse Fisiológico , Estresse Psicológico/fisiopatologia , Glândulas Suprarrenais/anatomia & histologia , Análise de Variância , Animais , Comportamento Animal , Cafeína/efeitos adversos , Cafeína/metabolismo , Estimulantes do Sistema Nervoso Central/efeitos adversos , Estimulantes do Sistema Nervoso Central/metabolismo , Corticosterona/sangue , Comportamento Exploratório , Feminino , Locomoção , Masculino , Aprendizagem em Labirinto , Tamanho do Órgão , Ratos , Ratos Wistar , Restrição Física , Caracteres SexuaisRESUMO
We studied the effect of chronic caffeine on parameters related to oxidative stress in different brain regions of stressed and non-stressed rats. Wistar rats were divided into three groups: control (receiving water), caffeine 0.3 g/L and caffeine 1.0 g/L (in the drinking water). These groups were subdivided into non-stressed and stressed (repeated restraint stress during 40 days). Lipid peroxide levels and the total radical-trapping potential were assessed, as well as antioxidant enzyme activities superoxide dismutase, gluthatione peroxidase, and catalase in hippocampus, striatum and cerebral cortex. Results showed interactions between stress and caffeine, especially in the cerebral cortex, since caffeine increased the activity of some antioxidant enzymes, but not in stressed animals. We concluded that chronic administration of caffeine led, in some cases, to increased activity of antioxidant enzymes. However, these effects were not observed in the stressed animals.