Involvement of oxytocin and GABA in consolation behavior elicited by socially defeated individuals in mandarin voles.

ABSTRACT

Consolation, which entails comforting contact directed toward a distressed party, is a common empathetic response in humans and other species with advanced cognition. Here, using the social defeat paradigm, we provide empirical evidence that highly social and monogamous mandarin voles (Microtus mandarinus) increased grooming toward a socially defeated partner but not toward a partner who underwent only separation. This selective behavioral response existed in both males and females. Accompanied with these behavioral changes, c-Fos expression was elevated in many of the brain regions relevant for emotional processing, such as the anterior cingulate cortex (ACC), bed nucleus of the stria terminalis, paraventricular nucleus (PVN), basal/basolateral and central nucleus of the amygdala, and lateral habenular nucleus in both sexes; in the medial preoptic area, the increase in c-Fos expression was found only in females, whereas in the medial nucleus of the amygdala, this increase was found only in males. In particular, the GAD67/c-Fos and oxytocin (OT)/c-Fos colocalization rates were elevated in the ACC and PVN, indicating selective activation of GABA and OT neurons in these regions. The "stressed" pairs matched their anxiety-like behaviors in the open-field test, and their plasma corticosterone levels correlated well with each other, suggesting an empathy-based mechanism. This partner-directed grooming was blocked by pretreatment with an OT receptor antagonist or a GABAA receptor antagonist in the ACC but not by a V1a subtype vasopressin receptor antagonist. We conclude that consolation behavior can be elicited by the social defeat paradigm in mandarin voles, and this behavior may be involved in a coordinated network of emotion-related brain structures, which differs slightly between the sexes. We also found that the endogenous OT and the GABA systems within the ACC are essential for consolation behavior in mandarin voles.