Acute naloxone-precipitated morphine withdrawal elicits nausea-like somatic behaviors in rats in a manner suppressed by N-oleoylglycine

Erin M. Rock, Samantha M. Ayoub, Cheryl L. Limebeer, Alexia Gene, Kiri L. Wills, Marieka V. DeVuono, Reem Smoum, Vincenzo Di Marzo, Aron H. Lichtman, Raphael Mechoulam, Linda A. Parker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Rationale: Acute naloxone-precipitated morphine withdrawal (MWD) produces a conditioned place aversion (CPA) in rats even after one or two exposures to high-dose (20 mg/kg, sc) morphine followed 24-h later by naloxone (1 mg/kg, sc). However, the somatic withdrawal reactions produced by acute naloxone-precipitated MWD in rats have not been investigated. A recently discovered fatty acid amide, N-oleoylglycine (OlGly), which has been suggested to act as a fatty acid amide hydrolase (FAAH) inhibitor and as a peroxisome proliferator-activated receptor alpha (PPARα) agonist, was previously shown to interfere with a naloxone-precipitated MWD-induced CPA in rats. Objectives: The aims of these studies were to examine the somatic withdrawal responses produced by acute naloxone-precipitated MWD and determine whether OlGly can also interfere with these responses. Results: Here, we report that following two exposures to morphine (20 mg/kg, sc) each followed by naloxone (1 mg/kg, sc) 24 h later, rats display nausea-like somatic reactions of lying flattened on belly, abdominal contractions and diarrhea, and display increased mouthing movements and loss of body weight. OlGly (5 mg/kg, ip) interfered with naloxone-precipitated MWD-induced abdominal contractions, lying on belly, diarrhea and mouthing movements in male Sprague–Dawley rats, by both a cannabinoid 1 (CB1) and a PPARα mechanism of action. Since these withdrawal reactions are symptomatic of nausea, we evaluated the potential of OlGly to interfere with lithium chloride (LiCl)-induced and MWD-induced conditioned gaping in rats, a selective measure of nausea; the suppression of MWD-induced gaping reactions by OlGly was both CB1 and PPARα mediated. Conclusion: These results suggest that the aversive effects of acute naloxone-precipitated MWD reflect nausea, which is suppressed by OlGly.

Original languageAmerican English
Pages (from-to)375-384
Number of pages10
JournalPsychopharmacology
Volume237
Issue number2
DOIs
StatePublished - 1 Feb 2020

Bibliographical note

Funding Information:
The research described here was funded by research grants from the Natural Sciences and Engineering Council of Canada (NSERC: 03629), Canadian Institutes of Health Research (CIHR:388239) and a research contract from PlantExt to Linda A Parker.

Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

  • Acute naloxone-precipitated morphine withdrawal
  • CB
  • Gaping
  • N-oleoylglycine
  • Nausea
  • PPARα
  • Rats
  • Somatic MWD

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