N- Oleoylglycine and N-Oleoylalanine Do Not Modify Tolerance to Nociception, Hyperthermia, and Suppression of Activity Produced by Morphine

Erin M Rock; Cheryl L Limebeer; Megan T Sullivan; Marieka V DeVuono; Aron H Lichtman; Vincenzo Di Marzo; Raphael Mechoulam; Linda A Parker

doi:10.3389/fnsyn.2021.620145

N- Oleoylglycine and N-Oleoylalanine Do Not Modify Tolerance to Nociception, Hyperthermia, and Suppression of Activity Produced by Morphine

Front Synaptic Neurosci. 2021 Mar 9:13:620145. doi: 10.3389/fnsyn.2021.620145. eCollection 2021.

Authors

Erin M Rock¹, Cheryl L Limebeer¹, Megan T Sullivan¹, Marieka V DeVuono¹, Aron H Lichtman², Vincenzo Di Marzo^{3

4}, Raphael Mechoulam⁵, Linda A Parker¹

Affiliations

¹ Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada.
² Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, United States.
³ Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Richerche, Naples, Italy.
⁴ Canada Excellence Research Chair on the Gut Microbiome/Endocannabinoidome Axis in Metabolic Health, Faculty of Medicine and Faculty of Agriculture and Food Science, CRIYUCPQ, INAF and Centre NUTRISS, Université Laval, Quebec City, QC, Canada.
⁵ Medical Faculty, Institute for Drug Research, Hebrew University, Jerusalem, Israel.

Abstract

The endogenous amide N-Oleoylglycine (OlGly) and its analog N-Oleoylalanine (OlAla), have been shown to interfere with the affective and somatic responses to acute naloxone-precipitated MWD in male rats. Here we evaluated the potential of a single dose (5 mg/kg, ip) which alleviates withdrawal of these endogenous fatty acid amides to modify tolerance to anti-nociception, hyperthermia, and suppression of locomotion produced by morphine in male Sprague-Dawley rats. Although rats did develop tolerance to the hypolocomotor and analgesic effects of morphine, they did not develop tolerance to the hyperthermic effects of this substance. Administration of neither OlGly nor OlAla interfered with the establishment of morphine tolerance, nor did they modify behavioral responses elicited by morphine on any trial. These results suggest that the effects of OlGly and OlAla on opiate dependence may be limited to naloxone-precipitated withdrawal effects.

Keywords: N-oleoylalanine; N-oleoylglycine; analgesia; morphine; tolerance.