Oleoyl glycine: interference with the aversive effects of acute naloxone-precipitated MWD, but not morphine reward, in male Sprague–Dawley rats

Gavin N. Petrie, Kiri L. Wills, Fabiana Piscitelli, Reem Smoum, Cheryl L. Limebeer, Erin M. Rock, Ashlyn E. Humphrey, Madeleine Sheppard-Perkins, Aron H. Lichtman, Raphael Mechoulam, Vincenzo Di Marzo, Linda A. Parker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Rationale: Oleoyl glycine (OlGly), a recently discovered fatty acid amide that is structurally similar to N- acylethanolamines, which include the endocannabinoid, anandamide (AEA), as well as endogenous peroxisome proliferator-activated receptor alpha (PPARα) agonists oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), has been shown to interfere with nicotine reward and dependence in mice. Objectives and methods: Behavioral and molecular techniques were used to investigate the ability of OlGly to interfere with the affective properties of morphine and morphine withdrawal (MWD) in male Sprague–Dawley rats. Results: Synthetic OlGly (1–30 mg/kg, intraperitoneal [ip]) produced neither a place preference nor aversion on its own; however, at doses of 1 and 5 mg/kg, ip, it blocked the aversive effects of MWD in a place aversion paradigm. This effect was reversed by the cannabinoid 1 (CB1) receptor antagonist, AM251 (1 mg/kg, ip), but not the PPARα antagonist, MK886 (1 mg/kg, ip). OlGly (5 or 30 mg/kg, ip) did not interfere with a morphine-induced place preference or reinstatement of a previously extinguished morphine-induced place preference. Ex vivo analysis of tissue (nucleus accumbens, amygdala, prefrontal cortex, and interoceptive insular cortex) collected from rats experiencing naloxone-precipitated MWD revealed that OlGly was selectively elevated in the nucleus accumbens. MWD did not modify levels of the endocannabinoids 2-AG and AEA, nor those of the PPARα ligands, OEA and PEA, in any region evaluated. Conclusion: Here, we show that OlGly interferes with the aversive properties of acute naloxone-precipitated morphine withdrawal in rats. These results suggest that OlGly may reduce the impact of MWD and may possess efficacy in treating opiate withdrawal.

Original languageAmerican English
Pages (from-to)2623-2633
Number of pages11
Issue number9
StatePublished - 1 Sep 2019

Bibliographical note

Funding Information:
Funding The research reported here was funded by research grants from the Natural Sciences and Engineering Research Council (NSERC 920157) and the Canadian Institutes for Health Research (CIHR 388239) to LAP, NIH grants R01DA039942, P30DA033934, and VCU School of Pharmacy start-up funds to AHL.

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


  • 2-Arachidonyl glycerol (2-AG)
  • Anandamide (AEA)
  • Conditioned place aversion (CPA)
  • Fatty acid amide hydrolase (FAAH)
  • Morphine withdrawal (MWD)
  • N-Arachidonoyl glycine (AraGly)
  • Oleoyl glycine (OlGly)
  • Oleoylethanolamide (OEA)
  • Palmitoylethanolamide (PEA)


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