Behavioral mechanisms underlying the maternal disruptive effect of serotonin 5-HT_2A receptor activation in Sprague–Dawley rats

Recent evidence indicates that acute activation of 5-HT_2A receptors causes a disruption of maternal behavior in rats. However, the behavioral mechanisms underlying such a disruption are not known. We addressed this issue using two behavioral approaches targeting the maternal motivational and emotional processing systems. First, we used the pup-separation technique to increase maternal motivation to see whether pup separation is capable of reducing the maternal disruptive effect of TCB-2 (a high-affinity 5-HT_2A agonist) treatment. On postpartum days 4 and 6, different groups of Sprague–Dawley dams were treated with the TCB-2 (5.0 mg/kg, sc) or vehicle and their maternal behaviors were tested after either a 4-h pup-separation or no-pup-separation condition. Although acute TCB-2 injection disrupted maternal behavior, this disruption was not attenuated by pup separation, even after we optimized the timing of separation to maximize its increase on maternal motivation. Acute TCB-2 also impaired the retrieval of food pellets, suggesting a general effect on motivated behaviors. Next, we used a pup preference test and found that dams treated with TCB-2 exhibited an even stronger preference to pups over a male conspecific than vehicle-treated dams, indicating an enhanced motivational and emotional processing of the rewarding property of pups. These findings suggest that TCB-2 has a disruptive effect on rat maternal behavior, and this disruption is not likely due to the drug’s effect on mothers’ motivational and emotional processing of the incentive salience of pups, although this motivational suppression account cannot be completely ruled out. Future work could explore other possible behavioral mechanisms, such as the drug’s effect on executive function.