Evitação social produzida pela exposição repetida ao estresse de derrota social: sinalização dopaminérgica e modulação por receptores CRF1 do fator liberador de corticotrofina

• Autor(a) principal: Favoretto, Cristiane Aparecida [UNIFESP]
• Data de Publicação: 2020
• Tipo de documento: Tese
• Idioma: por
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.xhtml?popup=true&id_trabalho=9106375; https://repositorio.unifesp.br/handle/11600/58774
• topic: Stress; Social behavior; Dopamine; Nucleus accumbens; Adrenocorticotropic Hormone; Estresse; Comportamento social; Dopamina; Núcleo accumbens; Hormônio liberador de corticotrofina; Motivação

Exposure to chronic social defeat stress may promote social investigation deficits, sometimes associated with other depressive-like behaviors (such as anhedonia and reduced motivation directed to rewards), in addition to altering dopaminergic signaling in the nucleus accumbens (NAc) of rodents. In NAc, as in other brain regions, dopaminergic receptors D1 and D2 seem to play different roles in responses to stress and social behavior. In addition, both dopaminergic mesolimbic function and social behaviors are modulated by corticotropin-releasing factor type 1 receptors (CRF1). In the present study, we aimed to investigate the consequences of repeated exposure to social defeat on accumbal dopamine release during social investigation and operant behavior for sucrose reinforcement. For this, male C57BL/6J mice were exposed to 10 days of social defeat and evaluated during social investigation and operant behavior for sucrose reinforcement, in fixed ratio 1 (FR-1) and progressive ratio (PR) schedules, while accumbal dopamine release was monitored using fast-scan cyclic voltammetry. In addition, we investigated the effects of treatments with D1, D2 or CRF1 receptor antagonists on the social investigation of mice exposed to social defeat. For this, Swiss male mice were exposed to social defeat and tested for social investigation after systemic treatment with selective antagonists. Our data showed that social defeat promoted social avoidance and an increased frequency of dopamine release events during social investigation. However, social stress did not induce changes in behavior or accumbal dopamine release during sucrose reinforcement tests. Social defeat stress also did not induce other depressive-like behaviors, such as decreased hedonic capacity, diminished self-care behavior and increased despair behavior. In addition, social investigation deficits were not altered by D1 receptors antagonism, but were attenuated by D2 receptors antagonism. CRF1 receptors antagonism seemed to intensify the social deficits promoted by social defeat. Our results suggest that exposure to social defeat induced changes in behavior and dopaminergic mesolimbic function that are selective to social contexts and social behaviors. In addition, social deficits induced by social defeat could be modulated by D2- and CRF1-mediated signaling. D1 receptors seem to be less related to social investigation behavior or social deficits induced by social defeat stress.