Serotonin 5-HT_2A and 5-HT_2C receptors regulate rat maternal behavior through distinct behavioral and neural mechanisms

Serotonin 5-HT_2A and 5-HT_2C receptors play important yet distinctive roles in the regulation of rat maternal behavior. The present study investigated their neural substrates and explored the possible behavioral mechanisms (i.e., behavioral organization or maternal motivation). Sprague-Dawley postpartum females were microinjected with either a selective 5-HT_2A agonist (TCB-2, 0.4 or 4.0 μg/side) or a 5-HT_2C agonist (MK212, 2.5 or 5.0 μg/side) into the medial prefrontal cortex (mPFC) or ventral tegmental area (VTA). Ten and 60 min later, their maternal activities were observed in the home cage; and their motivational responses towards pups were examined in a pup preference test and pup retrieval test throughout the first week of postpartum. In the mPFC, TCB-2 microinjection disrupted major components of maternal behavior (e.g., pup retrieval, pup crouching), as well as the sequential pup retrieval score (a measure of behavioral organization). In contrast, MK212 microinjection had a minimal disruption of maternal behavior. In the VTA, TCB-2 microinjection impaired pup retrieval, nest building, and pup crouching, whereas MK212 microinjection severely impaired pup retrieval, nest building and pup crouching. Moreover, only intra-VTA injection of MK212 significantly suppressed pup preference. Together, our data suggest that 5-HT_2A receptors in the mPFC and VTA may play an important role in the behavioral organization or executive control of maternal activities, but not in the motivational processing of the rewarding value of pups (maternal motivation). In contrast, 5-HT_2C receptors in the VTA play a critical role in maternal motivation, but not in the organization of maternal responses.