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Dissociable effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in the novelty-induced hypophagia test in mice

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Abstract

Rationale

Central CB1 cannabinoid receptors regulate anxiety-like and appetitive consummatory behaviors. Pharmacological antagonism/inverse-agonism of CB1 receptors increases anxiety and decreases appetitive behaviors; however, neither well-defined dose nor context dependence of these effects has been simultaneously assessed in one behavioral assay.

Objectives

We sought to determine the context and dose dependence of the effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in a model that allowed for simultaneous detection of anxiety-like and consummatory-related behaviors.

Methods

We determined the effects of the CB1 receptor antagonist/inverse-agonist, rimonabant, in the novelty-induced hypophagia (NIH) assay in juvenile male ICR mice.

Results

Rimonabant dose-dependently decreased consumption of a palatable reward solution completely independent of contextual novelty. Grooming and scratching behavior was also increased by rimonabant in a context-independent manner. In contrast, rimonabant increased feeding latency, a measure of anxiety-like behaviors, only in a novel, mildly anxiogenic context. The effects of rimonabant were specific since no effects of rimonabant on despair-like behavior were observed in the tail suspension assay. Blockade of CB2 receptors had no effect on novelty-induced increases in feeding latency or palatable food consumption.

Conclusions

Our findings indicate that CB1 receptor blockade decreases the hedonic value of palatable food irrespective of environmental novelty, whereas the anxiogenic-like effects are highly context-dependent. Blockade of CB2 receptors does not regulate either anxiety-like or consummatory behaviors in the NIH assay. These findings suggest that rimonabant modulates distinct and dissociable neural processes regulating anxiety and consummatory behavior to sculpt complex and context-dependent behavioral repertories.

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Acknowledgments

These studies were supported by the National Institute of Health MH090412 (S.P.). Behavioral studies were conducted at the Vanderbilt Neurobehavioral Core Facility.

Conflict of interest

The authors declare no financial conflicts of interest. The authors had full control of all data presented herein and will provide original data upon request.

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Authors and Affiliations

  1. Department of Psychiatry, Vanderbilt University School of Medicine, Robinson Research Building, Rm 724B, Nashville, TN, 37212, USA

    Joyonna C. Gamble-George, Jordan R. Conger, Nolan D. Hartley, Prerna Gupta, Joshua J. Sumislawski & Sachin Patel

  2. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Robinson Research Building, Rm 724B, Nashville, TN, 37212, USA

    Joyonna C. Gamble-George, Jordan R. Conger, Nolan D. Hartley, Prerna Gupta, Joshua J. Sumislawski & Sachin Patel

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  1. Joyonna C. Gamble-George
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  2. Jordan R. Conger
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Correspondence to Sachin Patel.

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Gamble-George, J.C., Conger, J.R., Hartley, N.D. et al. Dissociable effects of CB1 receptor blockade on anxiety-like and consummatory behaviors in the novelty-induced hypophagia test in mice. Psychopharmacology 228, 401–409 (2013). https://doi.org/10.1007/s00213-013-3042-8

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