Activation Of 5-hydroxytryptamine 1A Receptors Impairs Maternal Behavior In Postpartum Female Rats

Maternal behavior in rats is a highly motivated and well-organized social behavior.Many clinically used antipsychotic drugs,including the typical drug haloperidol and the atypical drugs clozapine,risperidone,olanzapine,quetiapine,aripiprazole,and amisulpride,disrupt active maternal responses(e.g.pup retrieval,pup licking,and nest building)to various extents.antipsychotic drugs at clinically relevant doses disrupt active maternal responses primarily by suppressing maternal motivation.Atypical drug-induced sedation also contributes to their disruptive effects,especially that on pup nursing.Among many potential receptor mechanisms,dopamine D2 receptors and serotonin 5-HT2A/2C receptors are shown to be critically involved in the mediation of the maternal disruptive effects of antipsychotic drugs,with D2 receptors contributing more to typical antipsychotic-induced disruptions,whereas 5-HT2A/2C receptors contributing more to atypical drug-induced disruptions.The nucleus accumbens shell-related reward circuitry is an essential neural network in the mediation of the behavioral effects of antipsychotic drugs on maternal behavior.This research not only helps understand the extent and mechanisms of impact of antipsychotic medications on human maternal care,but is also important for enhancing our understanding of the neurochemical basis of maternal behavior.It is also valuable for understanding the complete spectrum of therapeutic effects and side-effects of antipsychotic treatment.This knowledge may facilitate the development of effective intervening strategies to help patients coping with such undesirable effects.Objective:Given the known roles of serotonin(5-HT)in emotion,motivation,social behavior,and major depression-and its known interaction with dopamine-it is likely that serotonin also plays a crucial role in this behavior.So far,there are surprisingly few studies focusing on 5-HT in maternal behavior,except for maternal aggression.Serotonin 5-HT1A receptor has been extensively studied for its role in motivated behaviors.Previous work suggests that this receptor system plays a special role in rodent maternal aggression,but not in other aspects of maternal care(e.g.pup retrieval and nest building).The present study revisited this issue and assessed the basic effects of 5-HT1A activation or blockade on various maternal responses in postpartum female rats.We also examined the possible psychological functions underlying the effects of 5-HT1A in rat maternal behavior.Methods:Sprague-Dawley mother rats were given a single injection of a 5-HT1A agonist 8-OH-DPAT(0.1,0.5 or 1.0 mg/kg,sc),a 5-HT1A antagonist WAY-101405(0.1,0.5 or 1.0 mg/kg,sc)or 0.9%saline solution on postpartum days 3,5,and 7.Maternal behavior was tested 30 min before and 30 min,120 min,240 min after the injection.On PP8,pup preference test.Then pup separation test,PPI test and elevated plus maze test were conducted.Results:Acute and repeated injection of 8-OH-DPAT significantly disrupted pup retrieval,pup licking,nursing,and nest building in a dose-dependent fashion,whereas WAY-101405 had little effect at the tested doses.Subsequent pup preference test suggested that 8-OH-DPAT disrupted maternal behavior not by decreasing maternal affect or interest.The pup separation test and the pup retrieval test on an-elevated plus maze also suggested that this disruption was not due to any suppression on maternal motivation or motoric function.8-OH-DPAT did disrupt the prepulse-inhibition(a measure of sensorimotor gating,an attentional function)of acoustic startle response.Therefore,8-OH-DPAT might impair maternal care by interfering with the attentional processing.Clearly more work is needed to further determine the psychological mechanisms underlying the maternal disruptive effect of 5-HT1A receptor activation.Conclusion:Injection of 8-OH-DPAT significantly disrupted maternal behaveor in rats.This function was not produced by reducing maternal affect or interests,was not due to any suppression on maternal motivation or motoric function.May be it impaired maternal care by interfering with the attentional processing.The major conttributions of the present study lie in:We first use 5-HT1A receptor agonists and antagonists in the study of maternal behavior in rats then we try to use a number of behavioral methods to demonstrate its possible behavioral and psychological mechanisms.