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dc.contributor.authorBurke, Nikita N.
dc.contributor.authorFerdousi, Mehnaz
dc.contributor.authorDeaver, Daniel R.
dc.contributor.authorFinn, David P.
dc.contributor.authorRoche, Michelle
dc.contributor.authorKelly, John P.
dc.date.accessioned2019-04-03T08:40:01Z
dc.date.issued2018-12-13
dc.identifier.citationBurke, Nikita N., Ferdousi, Mehnaz, Deaver, Daniel R., Finn, David P., Roche, Michelle, & Kelly, John P. (2019). Locomotor and anti-immobility effects of buprenorphine in combination with the opioid receptor modulator samidorphan in rats. Neuropharmacology, 146, 327-336., doi: 10.1016/j.neuropharm.2018.12.012en_IE
dc.identifier.issn1873-7064
dc.identifier.urihttp://hdl.handle.net/10379/15092
dc.description.abstractModulation of the opioid system has re-emerged as a potential therapeutic avenue for treating depression, with efficacy of a fixed-dose combination of buprenorphine (BUP), a partial mu-opioid receptor (MOR) agonist and kappa-opioid receptor (KOR) antagonist, and samidorphan (SAM), a potent MOR antagonist, as an adjuvant treatment in patients with major depressive disorder (MDD). To advance understanding of the mechanism of action underlying this combination, we examined BUP, SAM and their combination in a series of rat behavioural assays. We examined effects on locomotor activity in Sprague Dawley (SD) rats over an extended period of time in a home-cage tracking system, and behavioural despair (immobility) in the forced swim test (FST), a commonly-used test to study antidepressants, in SD and Wistar-Kyoto (WKY) rats. Strain differences in opioid receptor and prepropeptide mRNA expression in the brain (prefrontal cortex, amygdala, hippocampus and striatum) were examined using qRT-PCR. BUP produced locomotor hyperactivity in SD rats from 2 to 6 h following administration, which was attenuated by SAM. In SD rats, a low, but not a high, dose of SAM in combination with BUP counteracted swim-stress induced immobility. This effect was not seen with BUP alone. In contrast, BUP alone reduced immobility in WKY rats, and this effect was enhanced by a low, but not high, dose of SAM. In WKY rats, MOR mRNA expression was higher in the hippocampus and lower in the striatum vs. SD rats. KOR mRNA expression was higher in the amygdala and nociceptin receptor (NOP) mRNA expression was lower in the hippocampus vs. SD rats. Differences in opioid receptor expression may account for the differential behavioural profile of WKY and SD rats. In summary, administration of BUP, a MOR receptor agonist together with a MOR opioid-receptor antagonist, SAM, reduces behavioural despair in animal models traditionally used to study effects of antidepressants.en_IE
dc.description.sponsorshipThis study was supported by an Industry-Academia collaboration with funding and samidorphan provided by Alkermes Inc; and a Strategic Partnership Programme Grant from Science Foundation Ireland and Alkermes Inc (14/SPP/B3051).en_IE
dc.formatapplication/pdfen_IE
dc.language.isoenen_IE
dc.publisherElsevieren_IE
dc.relation.ispartofNeuropharmacologyen
dc.subjectDepressionen_IE
dc.subjectBuprenorphineen_IE
dc.subjectOpioid receptoren_IE
dc.subjectOrced swim testen_IE
dc.subjectBehavioren_IE
dc.subjectmRNAen_IE
dc.subjectFORCED SWIMMING TESTen_IE
dc.subjectGENETIC ANIMAL-MODELen_IE
dc.subjectWISTAR-KYOTOen_IE
dc.subjectDEPRESSIVE BEHAVIORen_IE
dc.subjectBINDING PROPERTIESen_IE
dc.subjectSEROTONIN RELEASEen_IE
dc.subjectSTRESS-ULCERen_IE
dc.subjectMUen_IE
dc.subjectPOTENTen_IE
dc.subjectMORPHINEen_IE
dc.titleLocomotor and anti-immobility effects of buprenorphine in combination with the opioid receptor modulator samidorphan in ratsen_IE
dc.typeArticleen_IE
dc.date.updated2019-03-28T06:16:37Z
dc.identifier.doi10.1016/j.neuropharm.2018.12.012
dc.local.publishedsourcehttps://doi.org/10.1016/j.neuropharm.2018.12.012en_IE
dc.description.peer-reviewedpeer-reviewed
dc.contributor.funderAlkermes Incen_IE
dc.contributor.funderScience Foundation Irelanden_IE
dc.description.embargo2019-12-13
dc.internal.rssid15876452
dc.local.contactDavid Finn, Dept. Of Pharmacology &, Therapeutics, Nui, Galway. 5280 Email: david.finn@nuigalway.ie
dc.local.copyrightcheckedYes
dc.local.versionACCEPTED
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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