The Effect Of The Interaction Between Serotonin 2C Receptor And Dopamine D₂ Receptor On The Normal Expression Of Maternal Behavior

Maternal behavior is a highly motivated social behavior in rats,which has been used to study psychoactive drugs for neuroscience,clinical and pharmacological purposes.As we know,serotonin?5-HT?plays a modulatory role in social behavior,emotion and motivation.Besides,it also plays an important role in the interaction with dopamine in some aspects of pharmacological action mechanisms.Recently,more and more studies began to focus on the roles of different subtypes of serotonin receptors on the normal expression of maternal behavior.Some studies have also shown that different subtypes of serotonin receptors may indeed be involved in the regulation of maternal behavior,in particular serotonin 2C(5-HT_2C)receptors and serotonin 2A(5-HT_2A)receptors.And the rapid activation or inhibition of the 5-HT_2C receptor and the 5-HT_2A receptor revealed that 5-HT_2CC and 5-HT_2A receptors both significantly affect the normal expression of maternal maternal behavior.5-HT_2CC receptor agonists can inhibit the release of dopamine,but it is still unclear whether the 5-HT_2C receptor agonist disrupts maternal behavior by inhibiting the release of dopamine.That is,whether 5-HT_2CC receptor activation itself can destroy maternal behavior.Studies focused on the pharmacological,behavioral mechanisms and neuroanatomical on basis of this 5-HT_2C effect.It is widely accepted that MK212is involved in the regulation of important psychological processes?e.g.motivation,motor function?necessary for the normal expression of maternal behavior.MK212 is a highly selective 5-HT_2Cagonist,which can activate5-HT_2C receptors and then decrease dopamine?DA?release,to a certain degree.In recent years,studies on the involvement of dopamine in the regulation of maternal behavior have been more in-depth than the study of the involvement of serotonin in the regulation of maternal behavior.Many studies have shown that dopamine has an important regulatory role in maternal behavior,and mainly the dopamine D₂ receptor involved in the regulation of maternal behavior.Some studies also showed that the dopamine D₁ receptor also slightly regulate the expression of maternal behavior.However,there is still a lack of research on the effect of the interaction between serotonin2C receptor and dopamine D₂ receptor on the normal expression of maternal behavior.Quinpiroleis a selective D₂/D₃ agonist and haloperidol is primarily a D₂ receptor antagonist,singling injection of a certain dose of quinpirole or haloperidol significantly disrupts maternal maternal behavior.However,studies have shown that postpartum dams are treated with a combination of quinpirole and halopericol,then maternal behavioral expression of the dam will return to near normal levels.Based on the above experimental results,we thought that in the case of 5-HT_2C receptor agonist?MK212?in combination with D₂ receptor agonist?quinpirole?/D₂ receptor antagonist?haloperidol?,animal maternal behavior is Caused by quinpirole,but not by released endogenous dopamine.On this condition,if the 5-HT_2CC receptor agonist can still destroy the maternal behavior,it is postulated thatthe serotonin 2C receptor agonist itself can destroy the maternal behavior not only by inhibiting endogeneous dopamine release,i.e.,5-HT_2C receptor agonists can inhibit maternal behavior without relying on inhibition of dopamine release.We therefore conducted three experiments on whether 5-HT_2C receptor agonists could inhibit maternal behavior without inhibiting dopamine release.We hypothesized that if there is an interaction between serotonin 2C receptor and dopamine D₂receptors on the normal expression of maternal behavior,i.e.,there will be some interactionon the combination of MK212 and quinpirole or haloperidol of the normal expression of maternal behavior.Thereforequinpirole may reverse the MK212 induced maternal behavior deficits and haloperidol may deteriorate the MK212 induced maternal behavior deficits to a certain degree.Experiment 1,we tested this hypothesis by co-administrating quinpirole?1.0mg/kg?or haloperidol?0.2mg/kg?together with MK212?1.0mg/kg?and examined whether quinpirole or haloperidol could reverse or worsen the effects of MK212 in the Homecage experimental paradigm.Maternal behavior were tested on postpartum Days 3,5 and 7?PP3,PP5,PP7?at the same time on each test day,on which maternal behavior was observed at 4 time points.Before the experiment,all the animals were put into the experimental room in the cage for 30 minutes.The first one wasafter the adaption as baseline,and the restswere carried outat 30,120,and 240min after the injections.The latency of each record was 20minutes and the interval of two drugs was 30 minutes.Experiment 2,we planned to explore whether different dose of quinpirole?0.3 mg/kg?0.5mg/kg and 1.0 mg/kg?could reverse the MK212-treated on maternal behavior deficit by Homecage.The basic experimental procedure was consistent with the Experiment 1,excepting that different doses of quinpirole was tested in this test instead of haloperidol.Experiment 3,we planned to focus on observing the basis of quinpirole reserve haloperidol-induced maternal care deficit,next the effect of MK212-treated on maternal behavior.We took a co-administrating pharmacological approach by using a selective D₂/D₃ agonist quinpirole?1.0mg/kg?,a primary dopamineD₂ receptor antagonism haloperidol?0.2mg/kg?and a selective 5-HT_2C agonist MK212?1.0mg/kg?.On Postpartum Day 3,we mainly observed the change of the dams'maternal behavior following a serious of above operation.On Postpartum Day 5,the dams were placed into locomotor chambersaccording to the above operation to observe how much time the dams spent to contact with their pups.On the test days?Postpartum Day 3 and 5?,all subjects were tested 4 times at different time points:the first maternal behavior test starting at 30 min before the haloperidol or vehicle administration as baseline and the other tests occurred at 30,120 and 240 min after MK212 or vehicle injection.All test drugs were injected withhaloperidol or vehicles.c.as the first injection at 30 min after the first video recording,the second administration time of quinpirole or vehicle at 10 min later following first injected,the third administration time of MK212 or vehicle were at 20 min after the second administration.The present study nearly demonstrates that the different dose of quinpirole can't reverseMK212 inhibited maternal behavior.However,quinpirole deepened the deficit of maternal behavior by MK212-treated to some extent.And on the basis of quinpirole reversed haloperidol-induced maternal behavior disruption,MK212-treated ones also dramaticallydisrupted the dams'maternal behavior.According to all above results,we initially infer that the effect of MK212 on maternal behavior may not be significantly related to the effects of quinpirole and halopericol on maternal maternal behavior,and that the destructive effect of MK212 on maternal behavior is not related to the release of dopamine receptors.Conclusions:5-HT_2C receptor agonists can inhibit maternal behavior independently of reducing dopamine release,in other words,5-HT_2C receptor agonism itself can destroy maternal behavior or be related to other mechanisms of action of 5-HT_2CC receptor agonism,so the mechanism by which 5-HT_2C receptor agonists inhibit maternal behavior remains not sure.