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

• Published in: Psychopharmacology Vol. 236; no. 9; pp. 2623 - 2633
• Main Authors: Petrie, Gavin N., Wills, Kiri L., Piscitelli, Fabiana, Smoum, Reem, Limebeer, Cheryl L., Rock, Erin M., Humphrey, Ashlyn E., Sheppard-Perkins, Madeleine, Lichtman, Aron H., Mechoulam, Raphael, Di Marzo, Vincenzo, Parker, Linda A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2019; Springer; Springer Nature B.V
• Subjects: Amygdala; Analysis; Anandamide; Aversion; Behavioral assessment; Biomedical and Life Sciences; Biomedicine; Cannabinoid CB1 receptors; Cortex (insular); Dependence; Drug dependence; Fatty acids; Glycine; Methods; Morphine; Naloxone; Neurophysiology; Neurosciences; Nucleus accumbens; Oleic acid; Original Investigation; Palmitoylethanolamide; Pharmacology/Toxicology; Prefrontal cortex; Psychiatry; Reinforcement; Reinstatement; Rodents; Tissue analysis; United States; N-Arachidonoyl glycine (AraGly); Fatty acid amide hydrolase (FAAH); Oleoyl glycine (OlGly); 2-Arachidonyl glycerol (2-AG); Conditioned place aversion (CPA); Palmitoylethanolamide (PEA); Oleoylethanolamide (OEA); Morphine withdrawal (MWD); Anandamide (AEA)
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-019-05237-9

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.