N-Oleoyl-glycine reduces nicotine reward and withdrawal in mice

Giulia Donvito, Fabiana Piscitelli, Pretal Muldoon, Asti Jackson, Rosa Maria Vitale, Enrico D'Aniello, Catia Giordano, Bogna M. Ignatowska-Jankowska, Mohammed A. Mustafa, Francesca Guida, Gavin N. Petrie, Linda Parker, Reem Smoum, Laura Sim-Selley, Sabatino Maione, Aron H. Lichtman*, M. Imad Damaj, Vincenzo Di Marzo, Raphael Mechoulam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageAmerican English
Pages (from-to)320-331
Number of pages12
JournalNeuropharmacology
Volume148
DOIs
StatePublished - Apr 2019

Bibliographical note

Funding Information:
This work was supported by NIH grants P01DA009789 , R01DA039942 , P30DA033934 (AHL); R01 DA032246 and P50DA039841 (MID), T32DA007027 (AJ), and startup funds from the VCU School of Pharmacy. NSERC ( 92056 ) and CIHR ( 137122 ) grants to LAP.

Funding Information:
This work was supported by NIH grants P01DA009789, R01DA039942, P30DA033934 (AHL); R01 DA032246 and P50DA039841 (MID), T32DA007027 (AJ), and startup funds from the VCU School of Pharmacy. NSERC (92056) and CIHR (137122) grants to LAP.

Publisher Copyright:
© 2018

Keywords

  • Cannabinoid receptor-1 (CB1)
  • Conditioned place preference (CPP)
  • Insular cortex
  • N-oleoyl glycine
  • Nicotine withdrawal
  • Peroxisome proliferator-activated receptor alpha (PPAR-α)

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