Activation of 5-HT1A autoreceptors in the dorsal raphe nucleus reduces the behavioral consequences of social defeat

In animal models, serotonin (5-HT) activity contributes to stress-induced changes in behavior. Syrian hamsters (Mesocricetus auratus) exhibit a stress-induced change in behavior in which social defeat results in increased submissive and defensive behavior and a complete loss of normal territorial aggression directed toward a novel, non-aggressive opponent. We refer to this defeat-induced change in agonistic behavior as conditioned defeat. In this study we tested the hypothesis that 5-HT activity in the dorsal raphe nucleus (DRN) contributes to the acquisition and expression of conditioned defeat. We investigated whether injection of the selective 5-HT1A agonist flesinoxan (200 ng, 400 ng, or 800 ng in 200 nl saline) into the DRN would reduce the acquisition and expression of conditioned defeat. Additionally, we investigated whether injection of the selective 5-HT1A antagonist WAY 100635 (400 ng in 200 nl saline) into the DRN would enhance the acquisition and expression of conditioned defeat following a sub-optimal social defeat experience. We found that injection of flesinoxan into the DRN before exposure to a 15-min social defeat reduced the amount of submissive and defensive behavior shown at testing. We also found that injection of flesinoxan into the DRN before testing similarly reduced submissive and defensive behavior. In addition, we found that WAY 100635 enhanced conditioned defeat when injected either before social defeat or before testing. These data support the hypothesis that the activity of 5-HT cells in the DRN, as regulated by 5-HT1A autoreceptors, contributes to the formation and display of conditioned defeat. Further, our results suggest that 5-HT release in DRN projection regions augments defeat-induced changes in social behavior.