The Roles Of Dopamine D₂ Receptor And Serotonin 5-HT_2A Receptor In Modulating Maternal Behaviors Of Postpartum Rats

Maternal behavior is important for the wellbeing of human and other mammalian species.It is also important for the normal development of the brain and psychological functions of the young.Previous research has documented that dopamine and serotonin,as two major neurotransmitters in the brain,play important roles in the regulation of maternal behavior in rats,but how they do it psychologically has not been well understood.Extensive brain and behavioral research has shown that there are intimate interactions between the dopaminergic and serotoninergic systems at multiple levels,from cell firing,neurotransmitter release to behavior.Much of their interaction is done via dopamine D₂ receptors and serotonin 5-HT_2A receptors,both of which have been implicated in rat maternal behavior independently,based on various neuropharmacological and behavioral studies.However,it is not clear whether these two receptors interact in the control of maternal behavior.Previous maternal behavior studies have often used the home cage maternal behavior observation,but this test cannot provide a detailed analysis of various psychological processes?e.g.,emotion,motivation?involved in the maternal behavior.The present study employed the pup preference test and home cage maternal behavior observation,examined how dopamine neurotransmission via D₂ receptors and serotonin neurotransmission via 5-HT_2AA receptors affect maternal behaviors,teased out the different psychological processes that might be affected by D₂ or 5-HT_2AA receptors,and explored their interactions in the regulation of maternal behaviors.In the first study,we validated the pup preference test to show that it can record the emotional and motivational responses towards pups and this response is elevated in mother rats in comparison to nulliparous females.Eighteen postpartum rats and sixteen nulliparous rats were tested for five consecutive days?postpartum day 4-8?with pups confined in a cylinder-shape cage made of transparent acrylic?top and bottom?with stainless metal bars spaced in between or without pups in an open-field arena or without pups?an empty cage?.A cube served as a novel object in the testing arena.The total time spent exploring the two stimuli during the 10 min period was recorded and pup preference is calculated as the ratio of time spent exploring the pup cage over the total amount of time spent exploring the cage and object.We found that on postpartum day 4,mother rats exhibited a significantly higher pup preference than virgin females when tested under the pup presence condition.They did not differ from the virgins when tested under no pup condition.The second study examined the individual effects of D₂ receptors and 5-HT_2AA receptors in regulating maternal behaviors.We activated or blocked the D₂/5-HT_2AA receptors in postpartum female rats and compared their performance in the home cage maternal behavior test and the pup preference test.Results showed that acute stimulation of D₂ receptors by quinpirole?0.5 and 1.0 mg/kg,sc?reduced the time spent on exploring pups,but increased the object exploration time,leading to a reduced pup preference ratio.This treatment of quinpirole also disrupted various maternal responses in the home cage,and the observed behaviors was out of control.In contrast,acute blockade of D₂ receptors by haloperidol?0.1 mg/kg,sc?only suppressed the pup retrieval in the home cage,but had no effect on pup preference,consistent with the notion that haloperidol has an inhibitory effect on maternal motivation.Acute stimulation of 5-HT_2A receptors by TCB-2?2.5 mg/kg,sc?also decreased the pup exploration time,disrupted pup preference and pup retrieval,and exhibited disorganized maternal responses in the home cage,while acute blockade of 5-HT_2A receptors by MDL100907?1.0 mg/kg,sc?had no effect on pup preference and home cage maternal behaviors.These results suggest that activation of D₂ receptors mainly suppresses affective process or executive function,while blockade of D₂ receptors suppresses maternal motivation.Activation of 5-HT_2A receptors may suppress emotional response to pups,and also disrupts executive functions of dams.The third study investigated the interactive effects of between D₂ receptors and5-HT_2AA receptors in regulation maternal behaviors.We explored how activation or blockade of 5-HT_2A receptors influences the D₂-mediated maternal behavior.Results showed that MDL100907?1.0 mg/kg,sc?did not alter the maternal disruptive effects of quinpirole?0.5 and 1.0 mg/kg,sc?or haloperidol?0.1 and 0.05 mg/kg,sc?on pup preference and home cage maternal behaviors.Conversely,quinpirole?1.0 mg/kg,sc?also did not change the maternal disruption of TCB-2?2.5 mg/kg,sc?in pup preference and home cage maternal behaviors.Interestingly,haloperidol?0.1 mg/kg,sc?reduced the disruption of TCB-2 in pup preference.These results show that there is an antagonistic effect between D₂ blockade and 5-HT_2A activation on maternal behavior,indicating an interesting receptor interaction on maternal behavior.In conclusion,the present study demonstrates that activation or blockade of D₂receptors disrupts maternal behavior:activating D₂ receptors may disrupt the affective process or executive function,while blocking D₂ receptors inhibits maternal motivation.Activation of 5-HT_2A receptors also disrupts maternal behavior by disrupt the affective process or executive function,but the blockade of 5-HT_2A receptors has no effect on maternal behavior.It also shows an interaction between D₂ receptors and 5-HT_2AA receptors,as blockade of D₂ receptors reverses the disruption of 5-HT_2A receptor agonist in pup preference.Scientifically,this study enhances our understanding of the neurophysiological and behavioral mechanisms of maternal behaviors,and also provides insights on the possible neuroreceptor mechanisms involved in postpartum mental disorders,such as postpartum depression,anxiety and psychosis.Future research will further examine the neurocircuits involved in the 5-HT_2A receptor effect in maternal behavior and its interaction with D₂ receptors.