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BIFUNCTIONAL MU OPIOID AND NOCICEPTIN/ORPHANIN FQ RECEPTOR AGONIST BU08028 SELECTIVELY DECREASES ALCOHOL DRINKING IN RHESUS MONKEYS

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abstract
Alcohol use disorder persists as a devastating public health problem; widely effective pharmacological treatments are needed. Evidence from rodent models suggests that stimulating NOP receptors can decrease ethanol drinking. We characterized the effects of MOP antagonist naltrexone, MOP agonist buprenorphine, bifunctional MOP/NOP agonist BU08028, and NOP agonist SCH 221510, in a translational nonhuman primate model of AUD. Female rhesus monkeys drank a 4% ethanol solution 6 hours 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 these drugs, naltrexone, BU08028, and buprenorphine were administered chronically using a model of pharmacotherapy assessment that incorporates clinical aspects of AUD and treatment. Acutely, buprenorphine, BU08028, and SCH 221510 selectively decreased ethanol intake; naltrexone decreased ethanol intake and food pellet deliveries. Chronically, effects of BU08028 and buprenorphine were maintained for several weeks without emergence of adverse effects. BU08028 was approximately 0.5 and 1.0 log units more potent in acute and chronic studies, respectively. These data demonstrate that bifunctional MOP/NOP agonists, which may have therapeutic advantages to MOP-selective drugs, can decrease alcohol drinking in nonhuman primates.
subject
alcohol
drug abuse
nociceptin
non human primates
opioids
contributor
Flynn, Shawn (author)
Czoty, Paul W (committee chair)
Ko, Mei-Chuan (committee member)
date
2019-05-24T08:35:53Z (accessioned)
2019-05-24T08:35:53Z (available)
2019 (issued)
degree
Neuroscience (discipline)
identifier
http://hdl.handle.net/10339/94000 (uri)
language
en (iso)
publisher
Wake Forest University
title
BIFUNCTIONAL MU OPIOID AND NOCICEPTIN/ORPHANIN FQ RECEPTOR AGONIST BU08028 SELECTIVELY DECREASES ALCOHOL DRINKING IN RHESUS MONKEYS
type
Thesis

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