Social status in zebrafish modulates the behavioral response to 5-HT2C receptor agonists and antagonists

The effects of previous social experiences on social behavior have been demonstrated across species both in cooperative and competitive contexts. In dominance-subordinate hierarchies, differences across social ranks have been observed in many different mechanisms. Dominance hierarchies interfere in defensive behavior, where subordinate animals present a greater defensive behavior, regarding potential threats ("anxiety-like behavior"), than dominant animals. The serotonergic system plays a key role in regulating and mediating threat responses, including 5-HT2 receptors in the types of proximal threat responses modulated by the stress of social defeat. We separated 148 adult zebrafish in pairs and allowed them to interact for five days; after that, the dominant-subordinate rank was determined, and animals were treated with a 5-HT_2C receptor agonist (MK-212) or antagonist (RS-102221) before being observed in the novel tank test. While MK-212 increased bottom-dwelling, erratic swimming, and freezing across all statuses, RS-102221 decreased these variables in dominants but increased them in subordinates. Moreover, the effects of MK-212 were larger in subordinates than in controls or dominants, suggesting a sensitization of the 5-HT_2C receptor.