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Disruption of CB1 receptor signaling impairs extinction of spatial memory in mice

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Abstract

Rationale

A growing body of in vitro and in vivo evidence indicates that a central endocannabinoid system, consisting of CB1 receptors and endogenous cannabinoids, modulates specific aspects of mnemonic processes. Previous research has demonstrated that either permanent or drug-induced disruption of CB1 receptor signaling interferes with the extinction of a conditioned fear response.

Objectives

In the present study, we evaluated whether the endocannabinoid system also plays a role in extinguishing learned escape behavior in a Morris water maze task.

Methods

CB1 (−/−) mice and mice repeatedly treated with 3 mg/kg of the CB1 receptor antagonist SR 141716 (Rimonabant) were trained to locate a hidden platform in the Morris water maze. Following acquisition, the platform was removed and subjects were assigned to either a massed (i.e., five consecutive sessions consisting of four 2-min trials/session) or a spaced (a single, 1-min trial every 2–4 weeks) extinction protocol.

Results

Strikingly, both 3 mg/kg SR 141716-treated mice and CB1 (−/−) mice continued to return to the target location across all five trials in the spaced extinction procedure, while the control mice underwent extinction by the third or fourth trial. In contrast, both the 3-mg/kg SR 141716-treated and CB1 (−/−) mice exhibited extinction in the massed extinction trial procedure.

Conclusions

These findings indicate that disruption of CB1 receptor signaling impairs extinction processes in the Morris water maze, thus lending further support to the hypothesis that the endocannabinoid system plays an integral role in the suppression of non-reinforced learned behaviors.

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Acknowledgements

This work was supported by NIH grants DA 015683, DA 03672, DA 09789, DA 07027, DA 06094 and the NIDA Center for Drug Abuse Research Small Grants Program. We thank Dr. Billy R. Martin for helpful discussions.

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  1. Department of Pharmacology and Toxicology, School of Medicine, Virginia Commonwealth University, P.O. Box 980613, Richmond, VA, 23298-0613, USA

    S. A. Varvel, E. A. Anum & A. H. Lichtman

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  1. S. A. Varvel
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  3. A. H. Lichtman
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Correspondence to A. H. Lichtman.

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Varvel, S.A., Anum, E.A. & Lichtman, A.H. Disruption of CB1 receptor signaling impairs extinction of spatial memory in mice. Psychopharmacology 179, 863–872 (2005). https://doi.org/10.1007/s00213-004-2121-2

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  • DOI: https://doi.org/10.1007/s00213-004-2121-2

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