Avaliação dos efeitos da retirada do etanol em curto e longo prazo sobre respostas comportamentais relacionadas à depressão e sobre células imunorreativas para a serotonina no núcleo mediano da rafe em ratos

Abstract

Abstinence from alcohol in dependent individuals promotes a set of physical and psychic signs and symptoms, some of them are related to depression. Several preclinical studies have used animal models of alcohol consumption followed by withdrawal to analyze changes resulting from alcohol use. The purpose of the present study was to determine whether shortterm and long-term withdrawals after chronic ethanol consumption would promote behavioral changes suggestive of depression in the open field (CA) test and forced swimming test (TNF), and whether changes in immunoreactivity of serotonina (5-HT) reactive cells in the median raphe nucleus (MRN). Wistar rats with approximately 60 days of life were submitted to increasing concentrations of ethanol as the only source of liquid diet or water, both with free access to feed. The experiments were divided into two stages: behavioral and immunostaining. In the behavioral stage, after 21 days of exclusive consumption of alcohol, it was replaced by water (withdrawal) and after 72 hours (short term withdrawal group; n = 7) or 21 days (long term withdrawal group; n=7), the animals were exposed to the CA test, and the animals' locomotor activity was assessed through the parameters of distance traveled and mean velocity, and compared with the control group (n = 4). On the following day, TNF was used to evaluate the climbing and immobility times, parameters used to verify depressive type behaviors. In the immunohistochemical stage, the brains of the animals submitted to chronic ethanol consumption for 21 days (chronic consumption group, n = 5) followed by the withdrawal of 72 hours (short term withdrawal group, n = 6) or 21 days (long term withdrawal group; n = 5) and the control group (n = 4), were submitted to immunohistochemistry to verify the labeling of 5-HT immunoreactive cells in MRN. In addition, the percentage of immunoreactive cell area for 5-HT (relative optical density) was determined. The behavioral data of CA did not show any change in the locomotor activity of the animals between the groups. As for TNF, the data showed a decrease in climbing time in the short-term (-34.6%) and long-term (-35.6%) and increased short-term (34.6%) and long term (33.3%), compared to the control group. In immunohistochemistry, no differences were observed in counting of immunoreactive cellular profiles for 5-HT in MRN between the control, chronic consumption, short-term withdrawal and long-term withdrawal groups. Analysis of the relative optical density showed an increase in the content of 5-HT in the short withdrawal group (81.7%) compared to the control group. Taken together, the data obtained demonstrate a depressor-like effect induced by short- and long-term withdrawals of ethanol that is unrelated to changes in the number of serotonergic cells, but may be related to an increase in the relative optical density of 5-HT in the MRN.