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Attenuation of anticipatory nausea in a rat model of contextually elicited conditioned gaping by enhancement of the endocannabinoid system

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Abstract

Rationale

Enhancement of the endocannabinoid (EC) system may reduce anticipatory nausea (AN).

Objectives

The experiments evaluated the potential of the dual fatty acid amide hydrolase (FAAH)/monoacylglycerol lipase (MAGL) inhibitor, JZL195, on its own and combined with anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) to reduce contextually elicited gaping, a measure of AN in rats.

Methods

Following four context lithium chloride (LiCl) pairings, rats were injected with vehicle (VEH) or JZL195 (10 mg kg–1, intraperitoneally) 105 min before an injection of VEH, 2-AG (1.25 mg kg–1), or AEA (5.0 mg kg–1). Fifteen minutes later, all rats were placed in the LiCl-paired context for 5 min and in a different context for a 15-min locomotor test. Whole brains were extracted for EC analysis. The potential of the CB1 antagonist, SR141716, to reverse the suppression of AN by both JZL195 and AEA and of the CB2 antagonist, AM630, to reverse the suppression of AN by JZL195 was then evaluated.

Results

JZL195 suppressed gaping and elevated AEA, palmitoylethanolamine, and oleoylethanolamide. As the suppression of gaping was reversed by SR141716, but not by AM630, the effect was CB1 mediated. The suppressive effect of JZL195 on gaping, as well as elevation of AEA and 2-AG, was amplified by pretreatment with either AEA or 2-AG. On its own, AEA, but not 2-AG, also suppressed gaping—an effect that was also prevented by CB1 antagonism.

Conclusions

JZL195 reduces AN primarily by acting as a FAAH inhibitor, but MAGL inhibition is also indicated.

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Acknowledgments

This study was supported by a research grant from the Natural Sciences and Engineering Council of Canada to L. Parker.

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Authors and Affiliations

  1. Department of Psychology and Neuroscience Graduate Program, University of Guelph, Guelph, ON, N1H 2W1, Canada

    Cheryl L. Limebeer, Erin M. Rock, Elizabeth Imhof, Kai Wang & Linda A. Parker

  2. Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA

    Rehab A. Abdullah & Aron H. Lichtman

Authors
  1. Cheryl L. Limebeer
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  2. Rehab A. Abdullah
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  3. Erin M. Rock
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  4. Elizabeth Imhof
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  5. Kai Wang
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  6. Aron H. Lichtman
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  7. Linda A. Parker
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Correspondence to Linda A. Parker.

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Limebeer, C.L., Abdullah, R.A., Rock, E.M. et al. Attenuation of anticipatory nausea in a rat model of contextually elicited conditioned gaping by enhancement of the endocannabinoid system. Psychopharmacology 231, 603–612 (2014). https://doi.org/10.1007/s00213-013-3282-7

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  • DOI: https://doi.org/10.1007/s00213-013-3282-7

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