Blockade of serotonin 5-HT2A receptors potentiates dopamine D2 activation-induced disruption of pup retrieval on an elevated plus maze, but has no effect on D2 blockade-induced one

Abstract

Appetitive aspect of rat maternal behavior, such as pup retrieval, is motivationally driven and sensitive to dopamine disturbances. Activation or blockade of dopamine D₂ receptors causes a similar disruption of pup retrieval, which may also reflect an increase in maternal anxiety and/or a disruption of executive function. Recent work indicates that serotonin 5-HT_2A receptors also play an important role in rat maternal behavior. Given the well-known modulation of 5-HT_2A on the mesolimbic and mesocortical dopamine functions, the present study examined the extent to which blockade of 5-HT_2A receptors on dopamine D₂-mediated maternal effects using a pup retrieval on the elevated plus maze (EPM) test. Sprague-Dawley postpartum female rats were acutely injected with quinpirole (a D₂ agonist, 0.10 and 0.25 mg/kg, sc), or haloperidol (a D₂ antagonist, 0.1 or 0.2 mg/kg, sc), in combination of MDL100907 (a 5-HT_2A receptor antagonist, 1.0 mg/kg, sc, 30 min before quinpirole or haloperidol injection) or saline and tested at 30, 90 and 240 min after quinpirole or haloperidol injection on postpartum days 3 and 7. Quinpirole and haloperidol decreased the number of pup retrieved (an index of maternal motivation) and sequential retrieval score (an index of executive function), prolonged the pup retrieval latencies, reduced the percentage of time spent on the open arms (an index of maternal anxiety), and decreased the distance travelled on the maze in a dose-dependent and time-dependent fashion. MDL100907 treatment by itself had no effect on pup retrieval, but it exacerbated the quinpirole-induced disruption of pup retrieval, but had no effect on the haloperidol-induced one. These findings suggest a complex interactive effect between 5-HT_2A and D₂ receptors on one or several maternal processes (maternal motivation, anxiety and executive function), and support the idea that one molecular mechanism by which 5-HT_2A receptors mediate maternal behavior is through its modulation of D₂ receptors.

Keywords: Dopamine D(2); Haloperidol; MDL100907; Maternal behavior; Quinpirole; Serotonin 5-HT(2A).