Pharmacological characterization of neuromodulatory systems involved in biased social interaction toward stressed conspecifics in male rats

Group-living mammals can identify stress in conspecifics. When the male subject rats were allowed to interact with a pair consisting of a naïve stimulus rat and a shocked stimulus rat that had received foot shocks immediately before testing, they showed the biased social interaction toward shocked stimulus rats. Findings in the literature suggest roles for the oxytocin and other neuromodulatory systems in this biased interaction. However, the roles of the vasopressin, dopamine, and opioid systems remain unclear. Here we examined the effects of intraperitoneal administration of atosiban (an oxytocin receptor antagonist), SR49,059 (a vasopressin V1a receptor antagonist), haloperidol (a dopamine D2 receptor antagonist), naloxone (an opioid receptor antagonist), or vehicle, on this biased interaction. The vehicle-treated subjects showed longer interaction times toward shocked stimulus rats than toward naïve stimulus rats. This bias was abolished by atosiban, SR49,059, or haloperidol, whereas the naloxone-treated subjects retained the bias. These results suggest that oxytocin, vasopressin V1a, and dopamine D2 receptors, but not opioid receptors, contribute to biased interaction toward stressed conspecifics. Moreover, the naloxone-treated subjects showed an increased total interaction time, suggesting increased sociality. These findings contribute to a more comprehensive understanding of the neuromodulatory mechanisms underlying stress identification.