Avaliação do efeito da exposição de camundongos ao Teste de Exposição ao Rato sobre as respostas celulares e comportamentos relacionados a dependência de etanol

Abstract

The mental disorders involving stress and anxiety evokes different defensive behaviors against proximal or potential aversive stimuli to life. These disorders are risk factors to beginning and maintenance of abuse of drugs such as ethanol. Limbic system is responsible for coordinating these emotional responses. One of the main limbic system region is the extended amygdala, which contain central nucleus of amygdala and the bed nucleus of stria terminalis. Between the neurotransmitters involved, there are the neuropeptide Corticotrophin releasing factor (CRF) and cannabinoid system. Based on this information, this study aimed to analyze the effect of controlled exposure stress to a predator in relation to cellular and behavioral responses related to anxiety and ethanol seeking behaviors. The different models used to analyze anxiety was the Open Field Test (OFT) and the Elevated Plus Maze (EPM). On drug seeking behaviors, we used the Conditioned Place Preference (CPP), which evaluate the relationship between the place where the drug was administrated and its reinforcement; and the Operant Ethanol self-administration protocol, which evaluate the motivation to ethanol intake. The cellular response was measured by Fos protein a neuronal activation marker, and relative expression of CB1 and CRF1 receptors were measured by its mRNA in the amygdala. The results suggest that Central Amygdala neurons are more active after the stress exposition, as well as there are lower levels of CRF1 receptors expression and an increase in the CB1 receptors in the amygdala. In the behavioral tests, stressed animals exhibit anxiolytic effect on the CA, shown by higher time spent on the center of the apparatus and anxiogenic effect on EPM, shown by higher risk assessment behavior. Moreover, the same group showed up to be more responsive to the self-administration protocol, as the animals were more motivated to self-administrate ethanol. In the CPP experiment, although the animals developed the place preference, this effect was not intensified by stress, because all groups, even the non-stressed, developed the preference.