Effects of 5-hydroxytryptamine 2C receptor agonist MK212 and 2A receptor antagonist MDL100907 on maternal behavior in postpartum female rats

Maternal behavior in rats is a highly motivated and well-organized social behavior. Given the known roles of serotonin (5-HT) in emotion, motivation, social behavior, and major depression - and its known interaction with dopamine - it is likely that serotonin also plays a crucial role in this behavior. So far, there are surprisingly few studies focusing on 5-HT in maternal behavior, except for maternal aggression. In the present study, we examined the effects of 5-HT_2C receptor agonism and 5-HT_2A receptor antagonism on maternal behavior in postpartum female rats. We hypothesized that activation of 5-HT_2C receptors and blockade of 5-HT_2A receptors would produce a functionally equivalent disruption of maternal behavior because these two receptor subtypes often exert opposite effects on various brain functions and psychological processes relevant to rat maternal behavior. On postpartum Days 5, 7, and 9, Sprague-Dawley mother rats were given a single injection of 0.9% NaCl solution, the 5-HT_2C agonist MK212 (0.5, 1.0 or 2.0 mg/kg, ip), or the 5-HT_2A antagonist MDL100907 (0.05, 0.5 or 2.0 mg/kg, ip). Maternal behavior was tested 30 min before and 30 min, 120 min, 240 min after injection. Acute injection of MK212 significantly disrupted pup retrieval, pup licking, pup nursing, and nest building in a dose-dependent fashion. At the tested doses, MDL100907 had little effect on various components of rat maternal behavior. Across the 3 days of testing, no apparent sensitization or tolerance associated with repeated administration of MK212 and MDL100907 was found. We concluded that rat maternal performance is critically dependent on 5-HT _2C receptors, while the role of 5-HT_2A receptors is still inconclusive. Possible behavioral mechanisms of actions of 5-HT_2C receptor in maternal behavior are discussed.