8-OH-DPAT enhances dopamine D₂-induced maternal disruption in rats

Recent evidence indicates that 5-HT_1A receptors play a significant role in mediating maternal behavior in rats. Given that they also modulate the mesocortical dopamine system, we hypothesized that 5-HT_1A receptors may mediate maternal behavior, possibly by interacting with the D₂ receptor. To address this issue, we used a combination of 5-HT_1A agonist (8-OH-DPAT, 0.5 mg/kg) and two D₂ drugs (an agonist quinpirole, QUIN, 1.0 mg/kg; a potent D₂ antagonist haloperidol, HAL, 0.1 mg/kg) on rat maternal behavior in the home-cage maternal behavior and pup preference tests. We replicated the findings that acute QUIN, HAL, and 8-OH-DPAT disrupted home-cage maternal behavior. When administered in combination, pretreatment with HAL and QUIN worsened 8-OH-DPAT-induced maternal disruption and induced a decrease in the pup preference ratio. Accordingly, 8-OH-DPAT enhanced QUIN' and HAL's disruption of pup retrieval and pup preference, reversed the increase in hovering over pups induced by HAL. These findings suggest that activation of 5-HT_1A receptors enhances D₂-mediated maternal disruption. Furthermore, given that the combination of D₂ drugs and 5-HT_1A agonists only produced an additive effect on maternal disruption, 5-HT_1A receptors may have a direct effect on maternal behavior independent of their interaction with D₂ receptors.