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dc.contributor.authorHughes, Edel M.
dc.contributor.authorCalcagno, Patricia
dc.contributor.authorClarke, Morgane
dc.contributor.authorSanchez, Connie
dc.contributor.authorSmith, Karen
dc.contributor.authorKelly, John P.
dc.contributor.authorFinn, David P.
dc.contributor.authorRoche, Michelle
dc.date.accessioned2021-07-01T10:24:25Z
dc.date.available2021-07-01T10:24:25Z
dc.date.issued2020-01-21
dc.identifier.citationHughes, Edel M., Calcagno, Patricia, Clarke, Morgane, Sanchez, Connie, Smith, Karen, Kelly, John P., Finn, David P., Roche, Michelle. (2020). Prenatal exposure to valproic acid reduces social responses and alters mRNA levels of opioid receptor and pre-pro-peptide in discrete brain regions of adolescent and adult male rats. Brain Research, 1732, 146675. doi:https://doi.org/10.1016/j.brainres.2020.146675en_IE
dc.identifier.issn1872-6240
dc.identifier.issn0006-8993
dc.identifier.urihttp://hdl.handle.net/10379/16839
dc.description.abstractAltered social behaviours are a hallmark of several psychiatric and developmental disorders. Clinical and preclinical data have demonstrated that prenatal exposure to valproic acid (VPA), an anti-epileptic and mood stabiliser, is associated with impaired social responses, and thus provides a useful model for the evaluation of neurobiological mechanisms underlying altered social behaviours. The opioid system is widely recognised to regulate and modulate social behaviours, however few studies have examined if the endogenous opioid system is altered in animal models of social impairment. The present study examined social behavioural responses of adolescent and adult male rats prenatally exposed to VPA, and the expression of mRNA encoding opioid receptors and pre-pro-peptides in discrete brain regions. Adolescent and adult rats prenatally exposed to VPA spent less time engaging in social behaviours in the direct social interaction test and exhibited reduced sociability and social novelty preference in the 3-chamber sociability test, compared to saline-treated counterparts. The VPA-exposed adolescent rats exhibited significantly reduced kappa opioid receptor (oprk1) and pre-pro-dynorphin (pdyn) mRNA expression in the cerebral cortex, and reduced oprk1 and nociceptin/orphanin FQ (oprl1) mRNA expression in the hypothalamus. Adult rats prenatally exposed to VPA exhibited decreased mRNA expression of oprk1 and pdyn in hypothalamus, reduced pro-opiomelanocortin(pomc) in the striatum and an increase in delta opioid receptor (oprd1) mRNA in the amygdaloid cortex, when compared to saline-treated counterparts. Mu opioid receptor (oprm1) mRNA expression did not differ between saline and VPA-exposed rats in any region examined. The data demonstrate that impaired social behaviours in adolescent and adult rats prenatally exposed to VPA is accompanied by altered mRNA expression of opioid receptors and pre-pro-peptides in a region specific manner. In particular, both adolescent and adult VPA-exposed rats exhibit reduced oprk1-pdyn mRNA expression in several brain regions, which are associated with deficits in social behavioural responding in the model.en_IE
dc.description.sponsorshipThis study was supported by funding from Alkermes Inc., US and Science Foundation Ireland, Ireland (14/SPP/B3051).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofBrain Researchen
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/3.0/ie/
dc.subjectSocialen_IE
dc.subjectBehaviouren_IE
dc.subjectValproic aciden_IE
dc.subjectOpioid receptorsen_IE
dc.subjectDynorphinen_IE
dc.subjectKappaen_IE
dc.titlePrenatal exposure to valproic acid reduces social responses and alters mRNA levels of opioid receptor and pre-pro-peptide in discrete brain regions of adolescent and adult male ratsen_IE
dc.typeArticleen_IE
dc.date.updated2021-07-01T08:45:24Z
dc.identifier.doi10.1016/j.brainres.2020.146675
dc.local.publishedsourcehttps://doi.org/10.1016/j.brainres.2020.146675en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderAlkermes Inc.en_IE
dc.contributor.funderScience Foundation Irelanden_IE
dc.internal.rssid19609944
dc.local.contactMichelle Roche, Physiology, Rm2002 Human Biology Building, National University Of Ireland G, University Road. 5427 Email: michelle.roche@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionPUBLISHED
dcterms.projectinfo:eu-repo/grantAgreement/SFI/SFI Strategic Partnership Programme/14/SPP/B3051/IE/The opioid system as the brain's interface between cognition and motivation/en_IE
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