Avaliação dos efeitos da retirada do álcool a curto e longo prazo sobre comportamentos relacionados à ansiedade e marcação de células serotoninérgicas no núcleo dorsal da rafe de ratos

Abstract

Abusive use of alcohol is classified as a substance-induced disorder, capable of producing intoxication, withdrawal, and anxiety, possibly leading to relapse. Several studies have demonstrated the role of the serotonergic system as a modulator of behaviors related to anxiety and reward and alcohol dependence. Among serotonergic sources projecting to many brain areas, we can mention Dorsal raphe nucleus (DRN) and its portions. Therefore, the goal of this study was to investigate whether alcohol would alter the labeling of serotonergic cells in the dorsal (DRD) and ventral (DRV) portions of the NDR, in animals submitted to short (3 days) and long term (21 days) withdrawal, as well as continuous consumption and correlate the marking of the cells with behavioral states related to the anxiety generated by alcohol withdrawal. For this, two independent experiments were performed: in experiment 01 (behavioral stage), male Wistar rats were divided into 3 experimental groups, being a control group (water), 3 days withdrawn group and 21 days withdrawn group, all groups received chronic treatment with alcohol for 21 days. After a 3 days withdrawal and withdrawal of 21 days, animals were submitted to the elevated plus maze (EPM). Twenty-four hours later, they were submitted to the open field (OF) where anxietyrelated behaviors were assessed for 5 minutes. In the experiment 02 (immunohistochemical analysis) the groups mentioned above were added to the group that received continuous alcohol for 21 days, without withdrawal and followed the same treatment and withdrawal scheme. Then, it was performed a perfusion and immunohistochemistry test in the DRD and DRV portions of the DRN. Body weight and consumption of food and water-alcohol were monitored throughout the experimental period, for both experiments. In experiment 1, it was observed that alcohol withdrawal for 3 or 21 days altered neither the conventional and ethological parameters related to anxiety in the EPM and OF, nor the locomotion in EPM. In Experiment 2, it was observed that alcohol withdrawal for 3 or 21 days and continuous consumption did not change the immunoblot of serotonergic cells in both the observed portions. However, a significant increase in cell density was observed for the 3 day withdrawn group. This study demonstrated that serotonergic neurotransmission may be affected by alcohol withdrawal, but this change was not related to anxiety-related behaviors.