Effects of stimulation of mu opioid and nociceptin/orphanin FQ peptide (NOP) receptors on alcohol drinking in rhesus monkeys

Shawn M. Flynn, Phillip M. Epperly, April T. Davenport, Gerta Cami-Kobeci, Stephen M. Husbands, Mei Chuan Ko, Paul W. Czoty

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Abstract

Alcohol 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.

Original languageEnglish
Number of pages9
JournalNeuropsychopharmacology
Volume2019
Early online date10 Apr 2019
DOIs
Publication statusPublished - 10 Apr 2019

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Effects of stimulation of mu opioid and nociceptin/orphanin FQ peptide (NOP) receptors on alcohol drinking in rhesus monkeys. / Flynn, Shawn M.; Epperly, Phillip M.; Davenport, April T.; Cami-Kobeci, Gerta; Husbands, Stephen M.; Ko, Mei Chuan; Czoty, Paul W.

In: Neuropsychopharmacology, Vol. 2019, 10.04.2019.

Research output: Contribution to journalArticle

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