Alterações comportamentais e neuroquímicas relacionadas à administração crônica de etanol e exposição ao estresse em camundongos

Abstract

Ethanol consumption is one of the biggest risk factors for world morbidity and mortality, once its dependence is a serious public health problem. In laboratory animals, some behaviors related to ethanol dependence can be investigated, like conditioned place preference (CPP) and the symptoms of withdrawal syndrome. Stress is a factor of major importance for beginning, maintenance and reinstatement of abuse psychoactive drugs and can regulate neurochemical alterations induced by chronic administration of these substances. The objective of this study was investigate the effects of forced swimming stress, concomitant to ethanol chronic administration (in liquid diet), on CPP and ethanol withdrawal syndrome, and its relation to alterations of dopaminergic and serotoninergic neurotransmission in mice. When we evaluate anxiety parameters during ethanol withdrawal, it was not found alterations in both elevated plus maze and open field (OF). However, exposure to ethanol alone induced reduction of exploratory activity in OF, correlating to increase of dopaminergic turnover (ratio between dopaminergic metabolites by dopamine) observed in prefrontal cortex (PFC), due to the same treatment. PFC alteration can still be responsible by increase of ethanol seeking, analyzed in the CPP procedure. Nevertheless, in nucleus acumbens (NAc), it was found reduction of dopaminergic turnover in animals exposed to stress alone, which may be predisposed to increase of ethanol CPP in this experimental group. In animals exposed concomitantly to ethanol and stress, it was not found alterations in both CPP as in dopaminergic turnover in PFC or NAc. Absence of alterations in this group may be related with increase of dopaminergic storage in amygdala. Thus, our study indicates that stress as well as ethanol induces dopaminergic alterations in different encephalic regions and this can be responsible by characteristic behaviors of withdrawal syndrome and ethanol seeking. Therefore, stress has an important role for ethanol addiction development and it is necessary more studies to understand the neurochemical pathways responsible by this interaction.