, Volume 233, Issue 10, pp 1823–1828 | Cite as

Attenuation of cue-induced reinstatement of nicotine seeking by URB597 through cannabinoid CB1 receptor in rats

  • Benoit Forget
  • Mihail Guranda
  • Islam Gamaleddin
  • Steven R. Goldberg
  • Bernard Le FollEmail author
Original Investigation



The endocannabinoid system is composed of endocannabinoids (such as anandamide), their target receptors (CB1 and CB2 receptors, CB1Rs and CB2Rs), the enzymes that degrade them (fatty-acid-amide-hydrolase (FAAH) for anandamide), and an endocannabinoid transporter. FAAH inhibition has been recently identified as having a critical involvement in behaviors related to nicotine addiction and has been shown to reduce the effect of nicotine on the mesolimbic dopaminergic system via CB1R and peroxisome proliferator-activated receptor alpha (PPARα). Thus, inhibition of FAAH may represent a novel strategy for smoking cessation, but its mechanism of action on relapse to nicotine seeking is still unknown.


The study aims to explore the mechanism of action of the inhibitor of FAAH activity, URB597, on relapse to nicotine seeking by evaluating the effect of the CB1R, CB2R, and PPARα antagonists on the attenuating effect of URB597 on cue-induced reinstatement of nicotine seeking in rats.


URB597 reduced cue-induced reinstatement of nicotine seeking, an effect that was reversed by the CB1R antagonist rimonabant, but not by the CB2R or PPARα antagonists AM630 and MK886, respectively.


These results indicate that URB597 reduces cue-induced reinstatement in rats through a CB1 receptor-dependent mechanism, and not via CB2R or PPARα. Since FAAH inhibition represent a novel and promising strategy for tobacco smoking cessation, dissecting how it produces its action may lead to a better understanding of the neurobiological mechanisms underlying nicotine addiction.


Nicotine Intravenous self-administration Rats Relapse Rimonabant URB597 



We thank A. Pushparaj for his help during the experiments and comments on the manuscript. The experiments comply with the current laws of Canada.

Compliance with ethical standards


This work was supported by a grant from the Heart and Stroke Foundation no. NA 6901.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Benoit Forget
    • 1
    • 2
  • Mihail Guranda
    • 1
  • Islam Gamaleddin
    • 1
    • 3
  • Steven R. Goldberg
    • 4
  • Bernard Le Foll
    • 1
    • 5
    • 6
    Email author
  1. 1.Translational Addiction Research Laboratory, Campbell Family Mental Health Research InstituteCentre for Addiction and Mental Health, CAMHTorontoCanada
  2. 2.Institut Pasteur, Unité de Neurobiologie Intégrative des Systèmes Cholinergiques, CNRS UMR 3571Paris Cedex 15France
  3. 3.Institute of Environmental Studies and ResearchAin Shams UniversityCairoEgypt
  4. 4.Preclinical Pharmacology Section, Behavioral Neurosciences Branch, Intramural Research ProgramNIDA, NIH, DHHSBaltimoreUSA
  5. 5.Alcohol Research and Treatment Clinic, Addiction Medicine Services, Ambulatory Care and Structured TreatmentsCAMHTorontoCanada
  6. 6.Departments of Family and Community Medicine, Pharmacology, Psychiatry, Institute of Medical SciencesUniversity of TorontoTorontoCanada

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