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dc.contributor.authorFlynn, Shawn M.
dc.contributor.authorEpperly, Phillip M.
dc.contributor.authorDavenport, April T.
dc.contributor.authorCami-Kobeci, Gerta
dc.contributor.authorHusbands, Stephen M.
dc.contributor.authorKo, Mei-Chuan
dc.contributor.authorCzoty, Paul W.
dc.date.accessioned2020-11-26T12:23:40Z
dc.date.available2020-11-26T00:00:00Z
dc.date.available2020-11-26T12:23:40Z
dc.date.issued2019-04-10
dc.identifier.citationFlynn SM, Epperly PM, Davenport AT, Cami-Kobeci G, Husbands SM, Ko MC, Czoty PW (2019) 'Effects of stimulation of mu opioid and nociceptin/orphanin FQ peptide (NOP) receptors on alcohol drinking in rhesus monkeys', Neuropsychopharmacology, 44 (8), pp.1476-1484.en_US
dc.identifier.issn0893-133X
dc.identifier.doi10.1038/s41386-019-0390-z
dc.identifier.urihttp://hdl.handle.net/10547/624679
dc.description.abstractAlcohol use disorder (AUD) persists as a devastating public health problem; widely effective pharmacological treatments are needed. Evidence from rodent models suggests that stimulating brain receptors for the neuropeptide nociceptin/orphanin FQ (NOP) can decrease ethanol drinking. We characterized the effects of the mu opioid peptide (MOP) receptor agonist buprenorphine and the buprenorphine analog (2S)-2-[(5R,6R,7R,14S)-N-cyclopropylmethyl-4,5-epoxy-6,14-ethano-3-hydroxy-6 methoxymorphinan-7-yl]-3,3-dimethylpentan-2-ol (BU08028), which stimulates MOP and NOP receptors, in a translational nonhuman primate model of AUD. Rhesus monkeys drank a 4% ethanol solution 6 h per day, 5 days per week via an operant behavioral panel in their home cages. To assess behavioral selectivity, monkeys responded via a photo-optic switch to earn food pellets. After characterizing the acute effects of BU08028 (0.001–0.01 mg/kg, i.m.) and buprenorphine (0.003–0.056 mg/kg, i.m.), the drugs were administered chronically using a model of pharmacotherapy assessment that incorporates clinical aspects of AUD and treatment. Acutely, both drugs decreased ethanol drinking at doses that did not affect food-maintained responding. During chronic treatment, effects of BU08028 and buprenorphine were maintained for several weeks without development of tolerance or emergence of adverse effects. BU08028 was ~0.5 and 1.0 log units more potent in acute and chronic studies, respectively. The selective NOP receptor agonist SCH 221510 also selectively decreased ethanol intakes when given acutely (0.03–1.0 mg/kg, i.m.), whereas the MOP antagonist naltrexone (1.7–5.6 mg/kg, i.m.) decreased both ethanol intake and food pellets delivered. These data demonstrate that bifunctional MOP/NOP agonists, which may have therapeutic advantages to MOP-selective drugs, can decrease alcohol drinking in nonhuman primates.en_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.urlhttps://www.nature.com/articles/s41386-019-0390-zen_US
dc.rightsYellow - can archive pre-print (ie pre-refereeing)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectMu opioid receptorsen_US
dc.titleEffects of stimulation of mu opioid and nociceptin/orphanin FQ peptide (NOP) receptors on alcohol drinking in rhesus monkeysen_US
dc.typeArticleen_US
dc.identifier.journalNeuropsychopharmacologyen_US
dc.date.updated2020-11-26T11:59:27Z
dc.description.notefull text from https://researchportal.bath.ac.uk/en/publications/effects-of-stimulation-of-mu-opioid-and-nociceptinorphanin-fq-pep


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