RESUMO
Increasing evidence indicates that sleep deprivation alters behavioural responses to various pharmacological agents which might be associated to changes in receptor systems. The present work addressed the effects of sleep deprivation and recovery on behavioural changes induced by MK-801, and investigated whether such effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an open field arena and elevated plus maze. A separate set of animals was sacrificed for [³H]MK-801 binding analysis in 40 brain regions. MK-801-induced hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD-induced increase in grooming was antagonized by the drug. Anxiolytic effects of 0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant differences among groups were found in NMDAR binding. These findings indicate that the combined effects of MK-801 and sleep deprivation and recovery interact in a complex fashion to affect rat behaviour. They further suggest that such effects cannot be attributed to altered NMDAR binding in brain.
Assuntos
Comportamento Animal/fisiologia , Encéfalo/metabolismo , Maleato de Dizocilpina/farmacologia , Atividade Motora/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Privação do Sono/metabolismo , Análise de Variância , Animais , Autorradiografia , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Accumulating evidence points to the mesolimbic and the nigrostriatal dopamine systems as critical to behavioral sensitization induced by several drugs of abuse. In the present study, we analyzed D1 and D2 binding to brain regions related to these dopaminergic systems during the expression of ethanol-induced behavioral sensitization. The first experiment was performed to demonstrate the effectiveness of the ethanol treatment schedule and challenge used to induce the expression of the behavioral sensitization phenomenon. The second experiment was conducted to study D1 and D2 alterations in several brain regions during the expression of this phenomenon. Mice were ip treated with ethanol or saline for 21 consecutive days and 24 h after the last injection they received an ethanol or a saline challenge injection. Five minutes later, the animals were observed in an open-field for locomotion quantification or were sacrificed and their brains were submitted to autoradiographic binding analyses. No differences among the groups were found for D1 binding levels in all the brain regions analyzed. However, ethanol-sensitized mice showed reduced levels of D2 binding in the olfactory tubercle when compared to the other groups. Our data suggest that D2 receptor changes in the olfactory tubercle seem to play an important role in the expression of ethanol-induced behavioral sensitization.
Assuntos
Comportamento Animal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Condutos Olfatórios/metabolismo , Receptores Dopaminérgicos/metabolismo , Análise de Variância , Animais , Autorradiografia/métodos , Benzazepinas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Antagonistas de Dopamina/farmacologia , Feminino , Locomoção/efeitos dos fármacos , Camundongos , Condutos Olfatórios/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Racloprida/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacosRESUMO
Oral dyskinesias are implicated in a series of neuropathologies and have been associated to an increase in oxidative stress. Several antioxidants, including vitamin E, decrease reserpine-induced oral dyskinesia (OD) in rodents and we have described a protective role of striatal catalase against the development of OD. The aim of this study was to verify the effects of vitamin C alone or in combination with vitamin E on reserpine-induced OD as well as to determine a possible role of catalase in the antidyskinetic property of these vitamins. Different doses of vitamin C attenuated reserpine-induced increase in OD. A similar treatment with an effective dose of vitamin C concomitant to an effective dose of vitamin E potentiated the antidyskinetic effect of both vitamins when administered alone. The administration of these vitamins alone produced an increase in striatal catalase activity that likewise was potentiated by their combined administration. In addition, the antidyskinetic property of vitamin E and vitamin C was abolished by a concomitant treatment with the catalase inhibitor aminotriazole. These results indicate a beneficial effect of these vitamins and reinforce the critical role of striatal catalase against the development of oral dyskinesias.