LONG-LASTING HYPNOTIC TOLERANCE AND BEHAVIORAL SENSITIVITY TO ETHANOL IN POST-DEPENDENT RATS

Exposure to repeated cycles of ethanol intoxication and withdrawal triggers long-lasting neural and behavioral plasticity in experimental animals that appear relevant for modeling human alcoholism, such as increased ethanol preference and behavioral sensitivity to stress. Also, ethanol exposure induces tolerance in human and experimental animals, and after repeated administration, behavioral sensitization. Here, we asked whether our experimental paradigm of prolonged intermittent cyclic exposure to ethanol vapor induces long-lasting changes in tolerance and its stimulant properties. Post-dependent and control rats were injected with a hypnotic dose of ethanol (3 g/kg) and the loss of righting refl ex (LORR) was recorded. Blood ethanol levels (BLA) were monitored and elimination rate was calculated. The effect on locomotor activity induced by acute ethanol challenge (0.5 mg/kg) was registered in habituated animals. Furthermore, we studied neuroplasticity in systems related to these behaviors. We find a signifi cant decrease of LORR and increased ethanol-induced locomotion in post-dependent animals, while BLA or ethanol metabolism was not different from controls. These results give further validity to the cyclic exposure paradigm as a model of ethanol dependence and support its value for treatment development.