Empatia em camundongos: avaliação do papel da amígdala e córtex cingulado anterior na modulação da ansiedade induzida pelo convívio com parceiro submetido a um modelo de estresse crônico

Abstract

Empathy is the ability to recognize the other's emotional state, being fundamental to social interaction and survival of the species. The study of empathy in rodents can be carried out using models that assess anxiety responses promoted by cohabitation with a chronic stress partner. Evidence has shown the amygdala and anterior cingulate cortex (ACC) involvement in anxiety-like behaviors and empathy. The present study investigated the role of the amygdala and the ACC in anxiety induced by living with a conspecific subjected to chronic restraint stress. Male Swiss mice were housed in pairs and lived for 28 days. On the 15th day, they were divided into two groups: stress and control. The stress group consisted of the stress and stress observer subjects (they shared the same housing box), being that the stress subject underwent stress sessions in the tube for 14 days for 1 hour in the presence of their partner living. The control group was presented by the control and observer control subjects (housed in the same housing box); none of the animals experienced stress. In the 29th day, in experiment 1, the stress observer and control observer subjects were submitted to the immunofluorescence protocol to verify neuronal activation by quantifying of FosB protein in the amygdala and ACC. In experiment 2, on the 24th day, the stress observer and control observer subjects underwent stereotaxic surgery to implant guide cannulas in the amygdala and ACC. On the 29th day, the animals received intra-amygdala or intra-ACC injection of saline or CoCl2 and, after 5 minutes, were evaluated in the elevated plus maze (EPM). The results revealed that living with conspecific in restraint stress did not alter the expression of positive cells for the Fos B protein in the amygdala; however, it promoted a decrease in FosB quantification in the ACC compared to animals that lived with control. Living with a pair in chronic stress led to a reduction in the percentage of entries (%OAE) and time spent in the open arms (% OAT), without changing the entries in the closed arms (CAE) of the EPM, in addition to the increase in% SAP (stretched attend posture) protected and the percentage of protected head-dipping. Amygdala inactivation with CoCl2 did not change %OAE, %OAT, and CAE. In contrast, the inactivation of ACC with CoCl2 displayed an increase in %OAE and %OAT, without altering CAE. Also, there was a decrease in protected head-dipping in animals that lived with a pair in chronic stress. Our results suggest that living with a pair submitted to chronic restraint stress raised increased responses related to anxiety in mice exposed to EPM. Amygdala inactivation was not able to mitigate the anxiety induced by living together; however, the inactivation of the ACC attenuated the anxiety like-behavior. These results are suggestive that ACC plays a significant role in anxiety induced by living with a pair subjected to chronic stress.