RESUMO
Clinical studies have shown a positive correlation between novelty-seeking behavior and the susceptibility to consume drugs of abuse. Although several animal studies have demonstrated this correlation with psychostimulants or morphine, studies with alcohol have shown conflicting results. The aim of this work was to investigate alcohol-induced motor effects in Wistar rats with different responses to novelty. Animals were classified as Low- (LR) or High-Responders (HR) to novelty, depending on their horizontal activity in an automated open field. Motor activity was recorded in naïve, saline, and alcohol-administered rats at different doses (0.1, 0.25, 0.5, 1.0, or 2.5 g/kg). Horizontal movements, rearings, and stereotyped behaviors were evaluated. After the behavioral test, animals were sacrificed and blood alcohol concentrations (BACs) were measured. Low (0.1 and 0.25 g/kg) and high (2.5 g/kg) alcohol doses decreased horizontal movements in LR animals, whereas 1.0 g/kg increased this parameter in HR rats. Rearings were increased by alcohol 1.0 g/kg in LR animals. In HR rats, alcohol doses of 0.5 and 1.0 g/kg also increased this parameter. Stereotyped behaviors were decreased by an alcohol dose of 2.5 g/kg in LR animals, but were increased by an intermediate dose (1.0 g/kg) in HR rats. Differences in horizontal movements and rearings were found between LR and HR animals at certain ethanol doses. Horizontal movements (0.25 g/kg) and rearings (0.5 g/kg) were lower in LR than HR rats; however, rearings were lower in HR than LR rats at 1.0 g/kg. BACs were similar between LR and HR rats at all ethanol doses. These findings suggest that HR rats are more responsive to the stimulant effects of intermediate alcohol doses, whereas LR animals are sensitive to low/high doses of the drug. Sensitivity to alcohol motor effects may substantially depend on the initial animal's response to a novel environment. The stimulant effects of alcohol may constitute important behavioral traits significantly associated with the rewarding properties of the drug.
Assuntos
Etanol/farmacologia , Atividade Motora/efeitos dos fármacos , Animais , Concentração Alcoólica no Sangue , Relação Dose-Resposta a Droga , Comportamento Exploratório/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Antecedentes: La exposición crónica al alcohol se asocia con procesos neurotóxicos y neurodegenerativos relacionados con disfunciones cognitivas y de memoria. El daño inducido por alcohol depende de los patrones de consumo de etanol. La exposición prolongada al alcohol induce daño en distintas regiones cerebrales (cortezas prefrontal, perirrinal, entorrinal y parahipocampal, tálamo, hipotálamo, hipocampo y cerebelo) en pacientes alcohólicos y modelos animales de alcoholismo. Sin embargo, no se han estudiado las regiones cerebrales asociadas con el circuito de reforzamiento y recompensa de drogas de abuso.Objetivo: Investigar si la exposición crónica al alcohol induce daño neurodegenerativo en el cerebro de la rata, en particular en el sistema mesocorticolímbico y la amígdala.Método: Ratas Wistar macho fueron expuestas a etanol (10% v/v) o agua por consumo oral durante 30 días y se les privó de la droga por 0, 24 y 48h. Los animales fueron sacrificados y se les extrajo la sangre troncal y el cerebro. Para evaluar el daño neurodegenerativo, se utilizó el marcador fluorescente Fluoro-Jade B. La concentración de alcohol en sangre se determinó por espectrofotometría.Resultados: Se observó un escaso número de células positivas a Fluoro-Jade en las cortezas piriforme y frontal de asociación, el caudado-putamen y el tálamo dorsal. No se encontraron diferencias entre el tratamiento crónico o la privación de alcohol versus el grupo control.Discusión y conclusión: La exposición crónica al alcohol no indujo neurodegeneración en las condiciones utilizadas en este estudio. Probablemente, las concentraciones de alcohol en sangre alcanzadas durante el tratamiento no fueron suficientes para inducir muerte celular.
Background: Chronic alcohol exposure is associated to neurotoxic and neurodegenerative mechanisms that lead to several cognitive and memory dysfunctions. Alcohol-induced damage depends on ethanol consumption patterns. Prolonged alcohol exposure induces damage in distinct brain regions (prefrontal, perirhinal, entorhinal and parahippocampal cortices, thalamus, hypothalamus, hippocampus and cerebellum) in both alcoholic patients and animal models of alcoholism. However, brain areas of the drug reinforcement and reward circuit have not been investigated.Objective: To investigate if chronic alcohol exposure induces neurodegenerative damage in the rat brain, particularly in the mesocorticolimbic system and the amygdala.Method: Male Wistar rats were exposed to ethanol (10% v/v) or water by oral consumption during 30 days. In another set of experiments, animals similarly treated with ethanol were withdrawn from the drug for 24 and 48 h. At the end of the treatments, animals were sacrificed, whole blood samples were obtained and the brains were removed. A fluorescence marker (Fluoro-Jade B) was used to assess neurodegenerative damage in the brain. Blood alcohol concentration was evaluated by spectrophotometry.Results: We observed a low number of Fluoro-Jade B positive cells in different brain regions, including the piriform cortex, frontal cortex of association, caudate-putamen and dorsal thalamus. No differences were found between chronic alcohol or ethanol withdrawn groups versus control animals.Discussion and conclusion: Our results suggest that chronic alcohol exposure does not induce neurodegeneration under the present experimental conditions. Alcohol blood concentrations attained during treatment may not be sufficient to induce cell death.
