TY - JOUR
T1 - Oleoyl glycine
T2 - interference with the aversive effects of acute naloxone-precipitated MWD, but not morphine reward, in male Sprague–Dawley rats
AU - Petrie, Gavin N.
AU - Wills, Kiri L.
AU - Piscitelli, Fabiana
AU - Smoum, Reem
AU - Limebeer, Cheryl L.
AU - Rock, Erin M.
AU - Humphrey, Ashlyn E.
AU - Sheppard-Perkins, Madeleine
AU - Lichtman, Aron H.
AU - Mechoulam, Raphael
AU - Di Marzo, Vincenzo
AU - Parker, Linda A.
N1 - Publisher Copyright: © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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.
AB - 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.
KW - 2-Arachidonyl glycerol (2-AG)
KW - Anandamide (AEA)
KW - Conditioned place aversion (CPA)
KW - Fatty acid amide hydrolase (FAAH)
KW - Morphine withdrawal (MWD)
KW - N-Arachidonoyl glycine (AraGly)
KW - Oleoyl glycine (OlGly)
KW - Oleoylethanolamide (OEA)
KW - Palmitoylethanolamide (PEA)
UR - http://www.scopus.com/inward/record.url?scp=85064538470&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00213-019-05237-9
DO - https://doi.org/10.1007/s00213-019-05237-9
M3 - مقالة
C2 - 30993360
SN - 0033-3158
VL - 236
SP - 2623
EP - 2633
JO - Psychopharmacology
JF - Psychopharmacology
IS - 9
ER -