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N-Oleoyl-glycine reduces nicotine reward and withdrawal in mice.
- Source :
-
Neuropharmacology [Neuropharmacology] 2019 Apr; Vol. 148, pp. 320-331. Date of Electronic Publication: 2018 Mar 19. - Publication Year :
- 2019
-
Abstract
- Cigarette smokers with brain damage involving the insular cortex display cessation of tobacco smoking, suggesting that this region may contribute to nicotine addiction. In the present study, we speculated that molecules in the insular cortex that are sensitive to experimental traumatic brain injury (TBI) in mice might provide leads to ameliorate nicotine addiction. Using targeted lipidomics, we found that TBI elicited substantial increases of a largely uncharacterized lipid, N-acyl-glycine, N-oleoyl-glycine (OlGly), in the insular cortex of mice. We then evaluated whether intraperitoneal administration of OlGly would alter withdrawal responses in nicotine-dependent mice as well as the rewarding effects of nicotine, as assessed in the conditioned place preference paradigm (CPP). Systemic administration of OlGly reduced mecamylamine-precipitated withdrawal responses in nicotine-dependent mice and prevented nicotine CPP. However, OlGly did not affect morphine CPP, demonstrating a degree of selectivity. Our respective in vitro and in vivo observations that OlGly activated peroxisome proliferator-activated receptor alpha (PPAR-α) and the PPAR-α antagonist GW6471 prevented the OlGly-induced reduction of nicotine CPP in mice suggests that this lipid acts as a functional PPAR-α agonist to attenuate nicotine reward. These findings raise the possibility that the long chain fatty acid amide OlGly may possess efficacy in treating nicotine addiction.<br /> (Copyright © 2018. Published by Elsevier Ltd.)
- Subjects :
- Animals
Brain Injuries, Traumatic metabolism
Cerebral Cortex metabolism
Conditioning, Classical drug effects
Glycine antagonists & inhibitors
Glycine pharmacology
Male
Mecamylamine pharmacology
Mice
Nicotine metabolism
Nicotine pharmacology
Oleic Acids antagonists & inhibitors
Oxazoles pharmacology
PPAR alpha agonists
PPAR alpha antagonists & inhibitors
Tobacco Use Disorder psychology
Tyrosine analogs & derivatives
Tyrosine pharmacology
Glycine analogs & derivatives
Nicotine antagonists & inhibitors
Oleic Acids pharmacology
Reward
Substance Withdrawal Syndrome prevention & control
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7064
- Volume :
- 148
- Database :
- MEDLINE
- Journal :
- Neuropharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 29567093
- Full Text :
- https://doi.org/10.1016/j.neuropharm.2018.03.020