5‑Hydroxytryptamine 2A receptor inverse agonist pimavanserin impairs maternal behavior in postpartum female rats

Maternal behavior is a highly motivated and well-organized social behavior. Although previous studies have shown that 5‑hydroxytryptamine 2A/2C (5-HT_2A/2C) receptors play an important role in mediating the expression of normal maternal behavior, the role of 5-HT_2A receptors in maternal behavior remains unclear. In the present study, the homecage maternal behavior test paradigm was used to investigate whether the low or constitutive (i.e., intrinsic or basal) activity of 5-HT_2A receptors influences the expression of normal maternal behavior. The inverse agonist pimavanserin (3, 6, and 12 mg/kg) and neural antagonist ketanserin (2.5 and 5 mg/kg) were used to induce the low or constitutive activity of 5-HT_2A receptors, respectively. The results showed that inverse agonism of 5-HT_2A receptors by pimavanserin slightly impaired maternal behavior in postpartum female rats, reflected by less time spent on nest building, and that ketanserin did not impair major components of maternal behavior. Furthermore, neither pimavanserin nor ketanserin impaired spontaneous locomotion. These data indicate that the reduced activity of 5-HT_2A receptors may impair the expression of normal maternal behavior and this effect is not due to a nonspecific sedative effect. Nevertheless, the constitutive activity of 5-HT_2A receptors in the absence of an endogenous agonist (i.e., serotonin) may be involved in the expression of normal maternal behavior.