Naturally Occurring Brown Voles Have Different Levels Of Social Formation And Regulation Of Neuroendocrine Mechanisms

Impairments in the ability to engage in healthy social interactions and to form stable social attachments are common characteristics of several mental health disorders,including depression,addiction,schizophrenia and autism spectrum disorsers(ASDs).Identifying the neurobiological and genetic mechanisms contributing to normative social function is essential for understanding these disorders as well as for identifying potential targets for pharmacological interventions.Social interaction is a ubiquitous part of life,affecting social,psychological,physiological,and behavioral functions.Mechanisms in the brain underlying social interaction remain unclear.But social interaction involves a complex set of processes including sensory detection of conspecifics,recognition of familiar individuals,and motivation to initiate proximity or contact.In addition,incompatible processes such as aversion or aggression must be suppressed.Studies in animal and human have uncovered roles of arginine vasopressin(AVP),oxytocin(OT)and dopamine(DA)systems in complex social interactions.However,most animal research has focused on the roles of AVP,OT and DA systems in social behavior related to reproduction,such as parental behavior and pair bond.Limited information is available on the effect of AVP,OT and DA on non-reproductive social interactions between adult individuals.Moreover,early social experience can have a long-term impact on offspring brain and behavior at adult.Changes in early social environment can lead to alterations of the AVP,OT and DA system that can result in systemic changes in physiological function that can manifest in social behavior related to reproduction,including parental behavior and pair bond.But the long-lasting effect of changes in early social environment on non-reproductive social interactions between adult individuals and related neruoendocrine mechanisms remain poorly understood.In addition,constructing a generalized model that accounts for the overall effects of central AVP,OT and DA on social behavior would be difficult,as these neuromodulators often have species-and/or sex-specific effects,and their actions vary across different brain regions.There is a substantial amount of evidence that manipulation of neuromodulators in the AVP,OT and DA systems can have dramatic and powerful effects on social behavior related to reproduction by acting within specific CNS sites.Studies suggest that social behavior might require AVP,OT and DA actions at yet to be identified brain regions where its receptors are present,including the nucleus accumbens(Nacc),medial amygdala nucleus(MeA)and so on.These regions are likely to participate as a complex network to orchestrate social behavior.Thus,is there relations between AVP,OT and DA system and animal's sociability?How could differences in early developmental environment confer enduing changes in AVP,OT and DA system and then affect animal's social behavior during adulthood?Which brain regions these systems affect social behavior?Thus,we investigated the mechanism of formation and regular social behavior using monogamous mandarin voles with complex sociability.The goals of the present study were three fold.First,we compared levels of central AVP,OT and DA system parameters in the brains of animals with natural high sociability and low sociability in male and female mandarin voles.Second,we investigate whether naturally occurring variations in levels of parental care may affect sociability and levels of AVP,OT and DA system parameters in male and female mandarin voles.Third,we determine whether OT has potential pro-social effects in the NAcc.And we assessed whether OT affect levels of anxiety and locomotion and whether the effects of OT on social preferences in the NAcc are sex dependent.(1)Naturally occurring differences in levels of sociability are associated with the levels of central DA,AVP and OT and the expression of DA(D1R and D2R),AVP(V1aR),OT(OTR)receptors:We found that high social voles displayed more OT-ir cells in the PVN and SON,and more TH-ir neurons in the VTA compared to low social voles.We also found that high social males displayed less AVP-ir cell in the PVN compared to low social males.On the other hand,we found high social voles exhibited higher levels of OTR in the NAcc high social males displayed less DIR and D2R expression than low social males in the NAcc,high social females showed less D2R expression in the NAcc and higher levels of D2R expression in the MeA than low social females.(2)Naturally occurring differences in levels of parental care are associated with and the levels of sociability and central levels of DA,AVP and OT and the expression of DA(D1R and D2R),AVP(V1aR),OT(OTR)receptors:The increase in sociability in both sexes following the high parental contact,indicates that early rearing experience could affect social behavior in non-reproductive context in the mandarin voles,as expected.At the same time,we found that voles received higher levels of parental care(HC)displayed higher OT-ir in the PVN and SON and greater TH-ir in the VTA compared with voles received lower levels of paretnal care(LC),and male offspring of HC parents displayed less AVP-ir cell in the PVN compared to male offspring of LC parents.Moreover,we also found that early higher parental contact significantly increased OTR mRNA expression in the NAcc in females and males,reduced the mRNA expression of DIR and D2R in the NAcc in males,suppressed D2R expression in the NAcc and increased D2R expression in the MeA in females.(3)Effects of nucleus accumbens oxytocin and its antagonist on social approach behavior:We observed that accumbal-OT peptide may exert a pro-social effect in a dose-dependent manner in male and female mandarin voles with low levels of sociability.The results showed that administration of 1 ng/side OT increased social preference,however this effect was not apparent at lower and higher doses in voles.Central application of OTR-A and,thus,blockade of OTRs in the Nacc dose-dependently attenuated social approach in male and female mandarin voles.Micro-infusions of a selective OTR-A at 10 ng and 100ng doses reduced social approach behavior;1 ng had no effect.However,we found no effect of OT or OTR-A at any dose(0.1-10ng/side or 1-100ng/side)tested in the open field test.In conclusion,we have characterized OT,AVP and DA system regulating social interaction in non-reproductive context in sex-specific and region-specific ways,and naturally occurring variations in early life experiences are related to adult OT,AVP and DA system functioning,in a sex-specific and region-specific manner.Thus,variations in central OT,AVP and DA system would result in sociability differences.Moreover,our results suggest that the Nacc is a region where OT facilitates naturally occurring social preferences in less social female and male mandarin voles in a non-reproductive context and in a dose-dependent way.This may provide insights into the mechanisms underlying sex biases in social dysfunction as well as be informative regarding differential treatment of social dysfunction in males versus females.