RESUMO
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.
Assuntos
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
This study examined the effects of two chronic stress regimens upon depressive-like behavior, A(1) and A(2A) adenosine receptor binding and immunocontent. Male rats were subjected to unpredictable chronic mild stress (UCMS) or to chronic restraint stress (CRS) for 40 days. Subsequently, depressive-like behaviors (forced swimming and consumption of sucrose) were evaluated, and A(1) adenosine or A(2A) adenosine receptors were examined in the hippocampus or striatum, respectively. UCMS animals demonstrated depressive-related behaviors (decrease in sucrose consumption and increased immobility in the forced swimming test). This group also presented increased A(1) adenosine receptor binding and immunoreactivity in hippocampus, as well as increased striatal A(2A) adenosine receptor binding in the striatum, without alteration in immunoreactivity. Conversely, the chronic restraint stress group displayed only an increase in A(1) adenosine receptor binding and no alteration in the other parameters evaluated. We suggest that the alteration in adenosine receptors, particularly the upregulation of striatal A(2A) adenosine receptors following UCMS, could be associated with depressive-related behavior.
Assuntos
Depressão/etiologia , Depressão/patologia , Hipocampo/metabolismo , Receptor A1 de Adenosina/metabolismo , Receptor A2A de Adenosina/metabolismo , Estresse Psicológico/complicações , Adenosina Desaminase/farmacologia , Análise de Variância , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hipocampo/efeitos dos fármacos , Técnicas In Vitro , Masculino , Ligação Proteica/efeitos dos fármacos , Purinérgicos/farmacocinética , Ratos , Ratos Wistar , Sacarose/administração & dosagem , Edulcorantes/administração & dosagem , Natação/psicologia , Fatores de Tempo , Trítio/farmacocinética , Xantinas/farmacocinéticaRESUMO
Caloric restriction (CR) has been shown to either decrease or prevent the progression of several age-related pathologies. In previous work, we demonstrated that CR modulates astrocyte functions, suggesting that CR may exert neuroglial modulation. Here, we investigated the effects of CR on hippocampal (Hc) and cortical (Cx) oxidative stress parameters of male Wistar rats. Our results showed that CR-fed rats had 17% less body weight gain after 12 weeks of treatment. CR improved locomotion performance, increased glutathione levels and decreased glutathione peroxidase activity and the production of reactive oxygen species. However, no changes were observed in lipid peroxidation, nitric oxide content and catalase activity. Single cell gel electrophoresis assay (comet assay) revealed a reduction in the extent of basal DNA damage upon CR. Our data suggest that dietary CR could induce both hippocampal and cortical modulation resulting in metabolic changes and as a consequence, significant improvement of cellular defense-associated parameters.
Assuntos
Restrição Calórica , Córtex Cerebral/metabolismo , Animais , Comportamento Animal , Ensaio Cometa , Dano ao DNA , Masculino , Atividade Motora/fisiologia , Oxirredução , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Adverse early life events, such as periodic maternal separation, may alter the normal pattern of brain development and subsequently the vulnerability to a variety of mental disorders in adulthood. Patients with a history of early adversities show higher frequency of post-traumatic stress disorder (PTSD). This study was undertaken to verify if repeated long-term separation of pups from dams would affect memory and oxidative stress parameters after exposure to an animal model of PTSD. Nests of Wistar rats were divided into intact and subjected to maternal separation (incubator at 32°C, 3 h/day) during post-natal days 1-10. When adults, the animals were subdivided into exposed or not to a PTSD model consisting of exposure to inescapable footshock, followed by situational reminders. One month after exposure to the shock, the animals were exposed to a memory task (Morris water maze) and another month later animals were sacrificed and DNA breaks and antioxidant enzymes activities were measured in the hippocampus. Rats exposed to shock or maternal separation plus shock showed long-lasting effects on spatial memory, spending more time in the opposite quadrant of the water maze. This effect was higher in animals subjected to both maternal separation and shock. Both shock and maternal separation induced a higher score of DNA breaks in the hippocampus. No differences were observed on antioxidant enzymes activities. In conclusion, periodic maternal separation may increase the susceptibility to the effects of a stressor applied in adulthood on performance in the water maze. Increased DNA breaks in hippocampus was induced by both, maternal separation and exposure to shock.
Assuntos
Modelos Animais de Doenças , Hipocampo/metabolismo , Privação Materna , Memória/fisiologia , Estresse Oxidativo/fisiologia , Transtornos de Estresse Pós-Traumáticos/metabolismo , Animais , Dano ao DNA/fisiologia , Feminino , Masculino , Gravidez , Ratos , Ratos Wistar , Transtornos de Estresse Pós-Traumáticos/psicologia , Fatores de TempoRESUMO
This study was carried out to ascertain the effects of maternal separation (3 h per day) of mothers from their pups in the neonatal period in rats, which has been suggested to induce a depressive-like state, would have long lasting effects on different parameters including hippocampal Na(+), K(+)-ATPase activity, NO production, free radical production and antioxidant enzymes activities in dams. Fourty-eight Wistar rats were divided into 3 groups: control, brief separation (10 min) and long separation (3 h). The neonatal interventions were done on postpartum days 1-10. At 35 days post-partum the dams were killed and the hippocampal Na(+), K(+)-ATPase activity were measured, as well as the activity of the antioxidant enzymes catalase, glutathione peroxidase, superoxide dismutase, free radicals production, and the production of nitric oxide. Hippocampal Na(+), K(+)-ATPase activity was decreased in the brief separated group and in dams subjected to 3 h separation from their pups. A reduction in nitric oxide levels in the hippocampus in dams of the long separated group was also observed. It is concluded that the withdrawal of pups from their mothers make the mothers more susceptible to the development of neurochemical alterations that could be related to depressive features.
Assuntos
Comportamento Animal , Depressão/patologia , Modelos Animais de Doenças , Animais , Depressão/psicologia , Feminino , Hipocampo/enzimologia , Hipocampo/metabolismo , Óxido Nítrico/biossíntese , Ratos , Ratos Wistar , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Prenatal stress (PS) and early postnatal environment may alter maternal care. Infant rats learn to identify their mother through the association between maternal care and familiar odors. Female Wistar rats were exposed to restraint stress for 30 min, 4 sessions per day, in the last 7 days of pregnancy. At birth, pups were cross-fostered and assigned to the following groups: prenatal non-stressed mothers raising non-stressed pups (NS:NS), prenatal stressed mothers raising non-stressed pups (S:NS), prenatal non-stressed mothers raising stressed pups (NS:S), prenatal stressed mothers raising stressed pups (S:S). Maternal behaviors were assessed during 6 postpartum days. On postnatal day (PND) 7, the behavior of male and female pups was analyzed in the odor preference test; and noradrenaline (NA) activity in olfactory bulb (OB) was measured. The results showed that restraint stress increased plasma levels of corticosterone on gestational day 15. After parturition, PS reduced maternal care, decreasing licking the pups and increasing frequency outside the nest. Female pups from the NS:S, S:NS, S:S groups and male pups from the S:S group showed no nest odor preference. Thus, at day 7, female pups that were submitted to perinatal interventions showed more impairment in the nest odor preference test than male pups. No changes were detected in the NA activity in the OB. In conclusion, repeated restraint stress during the last week of gestation reduces maternal care and reduces preference for a familiar odor in rat pups in a sex-specific manner.
Assuntos
Comportamento Animal , Odorantes , Efeitos Tardios da Exposição Pré-Natal , Caracteres Sexuais , Olfato/fisiologia , Estresse Psicológico/etiologia , Análise de Variância , Animais , Animais Recém-Nascidos , Cromatografia Líquida de Alta Pressão , Corticosterona/sangue , Eletroquímica , Feminino , Humanos , Masculino , Comportamento Materno/psicologia , Metoxi-Hidroxifenilglicol/metabolismo , Atividade Motora , Norepinefrina , Gravidez , Ratos , Ratos Wistar , Restrição Física/métodos , Estresse Psicológico/sangue , Estresse Psicológico/psicologiaRESUMO
Previous studies have shown sex-specific oxidative changes in spinal cord of rats submitted to chronic stress, which may be due to gonadal hormones. Here, we assessed total radical-trapping potential (TRAP), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and lipid peroxidation (evaluated by the TBARS test) in the spinal cord of ovariectomized (OVX) female rats. Female rats were subjected to OVX, and half of the animals received estradiol replacement. Animals were subdivided into controls and chronically stressed (for 40 days). Our findings demonstrate that chronic stress decreased TRAP, and increased SOD activity in spinal cord homogenates from ovariectomized female rats and had no effect on GPx activity. On the other hand, groups receiving 17ß-estradiol replacement presented a decreased GPx activity, but no alteration in TRAP and in SOD activity. No differences in the TBARS test were found in any of the groups analyzed. In conclusion, our results support the idea that chronic stress induces an imbalance between SOD and GPx activities, additionally decreasing TRAP. Estradiol replacement did not reverse the effects of chronic stress, but induced a decrease in GPx activity. Therefore, estradiol replacement in ovariectomized chronically stressed rats could make the spinal cord more susceptible to oxidative injury.
Assuntos
Estradiol/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Restrição Física/fisiologia , Medula Espinal/metabolismo , Estresse Psicológico/fisiopatologia , Animais , Feminino , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Ovariectomia , Ovário/fisiologia , Ratos , Ratos Wistar , Medula Espinal/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
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.
Assuntos
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
OBJECTIVE: To evaluate the effects of the administration of lithium to adult rats on brown (perirenal) and white (inguinal) adipose tissues and to assess whether methylphenidate modulates lithium effects. METHODS: Twenty-five adult male Wistar rats were fed with either regular or lithium-containing chow for 30 days. Between days 15 to 30 of treatment, animals received daily intraperitoneal administrations of either methylphenidate or saline. RESULTS: Lithium significantly reduced perirenal fat, and this effect was minimized by the administration of methylphenidate. There were no significant differences between the groups in terms of the effects of lithium on inguinal fat. CONCLUSION: Our findings suggest that different effects on white and brown tissue distribution may be involved in lithium-induced weight gain.
OBJETIVO: Avaliar como a administração de lítio afeta o tecido adiposo marrom (perirrenal) e branco (inguinal) e se o metilfenidato modula os efeitos do lítio. MÉTODOS: Vinte e cinco ratos Wistar adultos machos foram alimentados com ração normal ou contendo lítio por 30 dias. Entre os dias 15 e 30 de tratamento, os animais receberam doses intraperitoneais diárias de metilfenidato ou solução salina. RESULTADOS: A administração de lítio reduziu significativamente a gordura perirrenal. Esse efeito foi reduzido com a administração de metilfenidato. Não houve diferenças significativas entre os grupos em relação à gordura inguinal. CONCLUSÃO: Os achados sugerem que efeitos diferenciados sobre os tecidos adiposos marrom e branco podem estar envolvidos no ganho de peso induzido pelo tratamento com lítio.
RESUMO
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.
Assuntos
Antioxidantes/metabolismo , Cafeína/farmacologia , Estresse Oxidativo , Estresse Psicológico/metabolismo , Animais , Catalase/metabolismo , Córtex Cerebral/metabolismo , Corpo Estriado/metabolismo , Glutationa Peroxidase/metabolismo , Hipocampo/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Restrição Física , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Glutamate is an excitatory neurotransmitter involved in neuronal plasticity and neurotoxicity. Chronic stress produces several physiological changes on the spinal cord, many of them presenting sex-specific differences, which probably involve glutamatergic system alterations. The aim of the present study was to verify possible effects of exposure to chronic restraint stress and 17beta-estradiol replacement on [3H]-glutamate release and uptake in spinal cord synaptosomes of ovariectomized (OVX) rats. Female rats were subjected to OVX, and half of the animals received estradiol replacement. Animals were subdivided in controls and chronically stressed. Restraint stress or estradiol had no effect on [3H]-glutamate release. The chronic restraint stress promoted a decrease and 17beta-estradiol induced an increase on [3H]-glutamate uptake, but the uptake observed in the restraint stress +17beta-estradiol group was similar to control. Furthermore, 17beta-estradiol treatment caused a significant increase in the immunocontent of the three glutamate transporters present in spinal cord. Restraint stress had no effect on the expression of these transporters, but prevented the 17beta-estradiol effect. We suggest that changes in the glutamatergic system are likely to take part in the mechanisms involved in spinal cord plasticity following repeated stress exposure, and that 17beta-estradiol levels may affect chronic stress effects in this structure.
Assuntos
Estradiol/farmacologia , Ácido Glutâmico/metabolismo , Restrição Física , Medula Espinal/efeitos dos fármacos , Estresse Psicológico/metabolismo , Animais , Doença Crônica , Transportador 1 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/metabolismo , Transportador 3 de Aminoácido Excitatório/metabolismo , Feminino , Ovariectomia , Ratos , Ratos Wistar , Medula Espinal/metabolismo , Sinaptossomos/metabolismoRESUMO
Previous studies indicate that, in adulthood, neonatally handled rats consume more sweet food than nonhandled rats. The aim of the present study was to assess the effects of the chronic exposure to a palatable diet (chocolate) in adult neonatally handled rats. We measured the consumption of foods (standard lab chow and chocolate), body weight gain, abdominal fat deposition, and levels of plasma lipids, glucose, insulin, and corticosterone in adult neonatally handled (10 min/d, first 10 d of life) and nonhandled rats. We found an increased intake of chocolate in handled rats, but this consumption decreased over time. Handled male animals exhibited higher body weight, higher caloric efficiency, and lower triglyceride levels. Nonhandled females that were exposed long-term to the highly caloric diet had increased abdominal fat deposition compared with handled females. Overall female rats had increased abdominal fat deposition, higher total cholesterol and glucose levels, and lower insulin in comparison with males. Interestingly, chocolate consumption diminished the weight of the adrenal glands in both handled and nonhandled animals. These findings suggest that neonatal handling induces a particular metabolic pattern that is sex specific.
Assuntos
Envelhecimento/metabolismo , Comportamento Animal , Cacau , Doces , Metabolismo Energético , Comportamento Alimentar , Preferências Alimentares , Manobra Psicológica , Gordura Abdominal/metabolismo , Glândulas Suprarrenais/crescimento & desenvolvimento , Envelhecimento/sangue , Animais , Animais Recém-Nascidos , Glicemia/metabolismo , Peso Corporal , Corticosterona/sangue , Ingestão de Alimentos , Ingestão de Energia , Feminino , Habituação Psicofisiológica , Humanos , Insulina/sangue , Lipídeos/sangue , Masculino , Tamanho do Órgão , Ratos , Ratos Wistar , Fatores Sexuais , Fatores de TempoRESUMO
This study was undertaken to verify if repeated long-term separation from dams would affect the development of parameters related to post-traumatic stress disorder (PTSD) after animals are subjected to inescapable shock when adults. Wistar rats were subjected to repeated maternal separation during post-natal days 1-10. When adults, rats from both sexes were submitted to a PTSD model consisting of exposure to inescapable footshock, followed by situational reminders. We observed long-lasting effects of both interventions. Exposure to shock increased fear conditioning. Anxiety-like behavior was increased and exploratory activity decreased by both treatments, and these effects were more robust in males. Additionally, basal corticosterone in plasma was decreased, paralleling effects observed in PTSD patients. Levels of S100B protein in serum and cerebrospinal fluid (CSF) were measured. Levels in serum correlated with the effects observed in anxiety-like behavior, increasing in males exposed to shock, and presenting no effect in females. S100B in CSF was increased in females submitted to maternal separation during the neonatal period. These results suggest that, in rats, an early stress experience such as maternal separation may aggravate some effects of exposure to a stressor during adult age, and that this effect is sex-specific. Additionally, data suggest that the increased S100B levels, observed in serum, have an extracerebral origin, possibly mediated by an increase in the noradrenergic tonus. Increased S100B in brain could be related to its neurotrophic actions.
Assuntos
Comportamento Animal/fisiologia , Privação Materna , Fatores de Crescimento Neural/metabolismo , Proteínas S100/metabolismo , Caracteres Sexuais , Transtornos de Estresse Pós-Traumáticos/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Condicionamento Psicológico/fisiologia , Corticosterona/sangue , Modelos Animais de Doenças , Eletrochoque/efeitos adversos , Comportamento Exploratório/fisiologia , Medo/fisiologia , Feminino , Masculino , Gravidez , Ratos , Ratos Wistar , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
This study evaluated the effects of chronic stress and lithium treatments on oxidative stress parameters in hippocampus, hypothalamus, and frontal cortex. Adult male Wistar rats were divided into two groups: control and submitted to chronic variate stress, and subdivided into treated or not with LiCl. After 40 days, rats were killed, and lipoperoxidation, production free radicals, total antioxidant reactivity (TAR) levels, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were evaluated. The results showed that stress increased lipoperoxidation and that lithium decreased free radicals production in hippocampus; both treatments increased TAR. In hypothalamus, lithium increased TAR and no effect was observed in the frontal cortex. Stress increased SOD activity in hippocampus; while lithium increased GPx in hippocampus and SOD in hypothalamus. We concluded that lithium presented antioxidant properties, but is not able to prevent oxidative damage induced by chronic variate stress.