5-HT _2A receptors modulate dopamine D ₂ -mediated maternal effects

Serotonin 5-HT _2A receptors are expressed throughout the mesolimbic and mesocortical dopamine pathways, and manipulation of this receptor system has a profound impact on dopamine functions and dopamine-mediated behaviors. It is highly likely that 5-HT _2A receptors may also modulate the D ₂ -mediated maternal effects. The present study investigated this issue and also explored the possible behavioral mechanisms. We tested the effects of two D ₂ drugs (an agonist quinpirole: 0.5, 1.0 mg/kg, and a potent D ₂ antagonist haloperidol: 0.05, 0.10 mg/kg, sc) and their combinations with two 5-HT _2A drugs (a selective 5-HT _2A agonist TCB-2: 2.5 mg/kg, and 5-HT _2A antagonist MDL100907, 1.0 mg/kg, sc) on maternal behavior in Sprague-Dawley postpartum females. Individually, TCB-2 (2.5 mg/kg, sc) and quinpirole (0.5 and 1.0 mg/kg, sc) reduced pup preference and disrupted home-cage maternal behavior. In contrast, haloperidol (0.10 mg/kg, sc) only disrupted home-cage maternal behavior, but did not suppress pup preference. MDL100907 (1.0 mg/kg, sc) by itself had no effect on either pup preference or maternal behavior. When administered in combination, pretreatment of TCB-2 did not alter quinpirole's disruption of pup preference and home-cage maternal behavior (possibly due to the floor effect), however, it did enhance haloperidol's disruption of pup retrieval in the home cage. MDL100907 had no effect both quinpirole's and haloperidol's disruption of pup preference and home-cage maternal behavior. Interestingly, haloperidol attenuated TCB-2's disruptive effect on pup preference. These findings suggest that activation of 5-HT _2A receptors tends to enhance D ₂ -mediated maternal disruption, whereas blockade of 5-HT _2A receptors is less effective. They also suggest that 5-HT _2A receptors may have a direct effect on maternal behavior independent of their interaction with D ₂ receptors. The possible behavioral and neural mechanisms by which 5-HT _2A - and D2-mediated maternal effects and their interaction are discussed.