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Inhibition of monoacylglycerol lipase (MAGL) enhances cue-induced reinstatement of nicotine-seeking behavior in mice

Abstract

Rationale

Tobacco smoking is still a major population health issue. The endocannabinoid system has been shown to control drug-seeking behaviors. There are two main endocannabinoids: anandamide degraded by fatty acid amide hydrolase (FAAH) and 2-arachidonoylglycerol (2-AG) degraded by monoacylglycerol lipase (MAGL).

Objectives

The role of MAGL has only been explored recently, and so far, no study have been performed to evaluate the effects of MAGL inhibitor on nicotine reinforcing properties and cue-induced reinstatement of nicotine seeking.

Methods

Here, we investigated the effects of the MAGL inhibitor JZL184 on nicotine self-administration under fixed and progressive-ratio schedules of reinforcement and on cue-induced reinstatement of nicotine seeking in mice. We also evaluated the effects of JZL184 on food self-administration for possible non-specific effects.

Results

JZL184 (0, 8, and 16 mg/kg) did not affect food taking, nicotine taking, or motivation for nicotine. MAGL inhibition by JZL184 (16 mg/kg) increased reinstatement of previously extinguished nicotine seeking induced by presentation of nicotine-associated cues, but did not produce reinstatement on its own.

Conclusions

This study implicates involvement of 2-AG in nicotine-seeking behaviors.

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Acknowledgments

This research was supported by a grant from the Canadian Institutes of Health Research (CIHR) Operating Grant #MOP-123423.

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Correspondence to Bernard Le Foll.

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Ethical approval

All the experimental procedures described in this study were carried out in compliance with the guidelines of the Canadian Council on Animal Care and the Animal Care Committee at CAMH.

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Trigo, J.M., Le Foll, B. Inhibition of monoacylglycerol lipase (MAGL) enhances cue-induced reinstatement of nicotine-seeking behavior in mice. Psychopharmacology 233, 1815–1822 (2016). https://doi.org/10.1007/s00213-015-4117-5

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  • DOI: https://doi.org/10.1007/s00213-015-4117-5

Keywords

  • 2-arachidonoylglycerol
  • Nicotine
  • Reinstatement
  • Self-administration
  • Mice