Reduced consolation behaviors in physically stressed mandarin voles: involvement of oxytocin, dopamine D2 and serotonin 1A receptors within the anterior cingulate cortex

BACKGROUND: Consolation is a type of empathy-like behavior that has recently been observed in some socially living rodents. Despite the growing body of literature suggesting that stress affects empathy, the relationship between stress and consolation remains understudied at the preclinical level. Here, we examined the effects of chronic emotional stress (ES) or physical stress (PS) exposure on consolation and emotional behaviors by using the socially monogamous mandarin vole (Microtus mandarinus) in both males and females. METHOD/RESULTS: PS-voles were exposed to 14-day social defeat stress, whereas ES-voles vicariously experienced the defeat of their partners. We found that PS- but not ES-voles showed reduced grooming toward their defeated partners and increased anxiety- and despair-like behaviors. Meanwhile, PS-voles exhibited decreased neural activity in the anterior cingulate cortex (ACC), which is centrally involved in empathy. The densities of oxytocin receptors (OTRs), dopamine D2 receptors (D2Rs) and serotonin 1A-receptors (5-HT1ARs) within the ACC were significantly decreased in the PS group compared with controls. All the behavioral and physiological changes were similar between the sexes. Finally, we found that the reduced consolation behavior and some anxiety-like syndromes in PS-voles could be alleviated by pretreatment with an OTR, D2R or 5-HT1AR agonist within the ACC, whereas injections of corresponding receptor antagonists to the control voles decreased the consolation behavior and increased some anxiety-like behaviors. CONCLUSIONS: Our results indicated that chronic PS exposure impaired consolation and induced anxiety-like behaviors in mandarin voles and OTRs, 5-HT1ARs and D2Rs within the ACC may play important roles in these processes.