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The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat

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An Erratum to this article was published on 17 May 2011

Abstract

Rationale

Anticipatory nausea (AN) experienced by chemotherapy patients is resistant to current anti-nausea treatments. In this study, the effect of manipulation of the endocannabinoid (EC) system on a rat model of nausea (conditioned gaping) was determined.

Objective

The potential of cannabidiol (CBD) and the fatty acid amide hydrolase (FAAH) inhibitor, URB597 (URB) to reduce conditioned gaping in rats were evaluated.

Materials and methods

In each experiment, rats received four conditioning trials in which they were injected with lithium chloride immediately before placement in a distinctive odor-laced context. During testing, in experiment 1, rats were injected with vehicle (VEH), 1, 5 or 10 mg/kg CBD 30 min before placement in the context previously paired with nausea and in experiment 2, rats were injected with VEH, 0.1 or 0.3 mg/kg URB 2 h before placement in the context. Additional groups evaluated the ability of the CB1 antagonist/inverse agonist, SR141716A, to reverse the suppressive effects of URB. Experiment 3 measured the potential of URB to interfere with the establishment of conditioned gaping.

Results

When administered before testing, CBD (1 and 5, but not 10 mg/kg) and URB (0.3, but not 0.1 mg/kg) suppressed conditioned gaping. The effect of URB was reversed by pre-treatment with the CB1 antagonist/inverse agonist, SR141716A. When administered before conditioning, URB also interfered with the establishment of conditioned gaping.

Conclusions

Manipulations of the EC system may have therapeutic potential in the treatment of AN.

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Acknowledgments

This research was supported by a grant from the Natural Sciences and Engineering Research Council of Canada to LAP, the Israel Science Foundation and NIH to RM, NIH to DP and by a grant from Wilfrid Laurier University’s Student Technology Endowment Program and an Ontario Graduate Scholarship to EMR.

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Authors and Affiliations

  1. Department of Psychology, University of Guelph, Guelph, ON, N1G 2W1, Canada

    Erin M. Rock, Cheryl L. Limebeer & Linda A. Parker

  2. Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Hebrew University Medical Faculty, Jerusalem, 91120, Israel

    Raphael Mechoulam

  3. Department of Pharmacology, University of California, Irvine, CA, 92697, USA

    Daniele Piomelli

Authors
  1. Erin M. Rock
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  2. Cheryl L. Limebeer
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  3. Raphael Mechoulam
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  4. Daniele Piomelli
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  5. Linda A. Parker
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Corresponding author

Correspondence to Linda A. Parker.

Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/s00213-011-2332-2.

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Rock, E.M., Limebeer, C.L., Mechoulam, R. et al. The effect of cannabidiol and URB597 on conditioned gaping (a model of nausea) elicited by a lithium-paired context in the rat. Psychopharmacology 196, 389–395 (2008). https://doi.org/10.1007/s00213-007-0970-1

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  • DOI: https://doi.org/10.1007/s00213-007-0970-1

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