A inativação química do córtex cingulado anterior e da ínsula reverte a ansiedade em camundongos expostos ao modelo de empatia induzida pela nocicepção

Abstract

Empathy is characterized by the ability to recognize and respond to the emotional signals of others, being a crucial factor in the emotional experience and social interaction, allowing humans, as well as other species, to detect affective states of others. In this sense, recent studies have shown that cohabitation with an animal with chronic pain induces increased nociception and anxiety in the partner, that is, in the observer. These results reinforce the assumption that responses related to anxiety make it possible to identify the existence of emotional responses, which may be related to empathy. Evidence has suggested the involvement of the anterior cingulate cortex (ACC) and insula in the modulation of anxiety. However, no study has evaluated whether these structures participate in the increased anxiety factor observed in mice living with their partner with chronic pain. Thus, the aim of this study was to investigate the effects of reversible inactivation of ACC and insula on the modulation of anxiety induced by the empathy model in mice exposed to the elevated plus-maze (EPM). For this, male Swiss mice (n = 10-12/group), 21 days after birth, were housed in pairs to establish familiarity. On the 14th day of cohabitation, one of the animals of the pair underwent surgery for sciatic nerve constriction (NC) or surgery without nerve constriction (Sham). On the 23rd day, cagemates were submitted to stereotactic surgery for implantation of guide cannulas directed to the CCA (experiment 1) or to the insula (experiment 2). On the 28th day, cagemates (CNC and CS) that lived with their respective NC and Sham groups received bilateral intra-CCA or intra-insular saline or cobalt chloride (CoCl2) (reversible and non-selective synaptic blocker) injections, and after five minutes they were exposed to the EPM. The t test for independent samples showed that in Experiments 1 and 2, the NC mice submitted to the hot plate test showed decreased paw withdrawal latency when compared to the Sham mice. The two-way analysis of variance (ANOVA) followed by the Duncan test revealed that cohabitation with nociception mice produced an increased anxiety response in observers, confirming previous results in the literature. The chemical inactivation of the CCA and the insula produced an increased percentage of entries and time spent in the open arms, without altering the entries in the closed arms of the LCE. Furthermore, it also decreased the display of risk assessment behaviors, such as percentage of time in the center, percentage of head-dipping and percentage of protected stretched attend postures and total of stretched attend postures in experiment 1; and in experiment 2, decreased the percentage of head-dipping and protected stretched attend postures, and the total of head-dipping and stretched attend postures, which suggests a decrease in anxiety-like behaviors. The results suggest that the inactivation of the CCA and the insula reverses the display of anxiety-like behaviors in mice submitted to the empathy model evaluated in the LCE. In addition, they indicate that these structures are essential for the display of anxious behaviors induced by emotional contagion, assessed through cohabitation with animals subjected to neuropathic pain.