Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB 1 receptors

Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB 1 receptors The role of cannabinoid CB 1 receptors in the action of anxiolytics was examined. Deletion of CB 1 receptors resulted in increased anxiety-like behaviours in light/dark box, elevated plus maze and social interaction tests. Mutant mice presented basal low corticosterone concentrations and low proopiomelanocortin gene expression in the anterior lobe of the pituitary gland compared to wild-type mice. Ten minutes of restraint stress resulted in a twofold increase in corticosterone concentrations in the plasma of mutant mice, compared to wild-type mice. Bromazepam (50 or 100 μg/kg) markedly increased the time spent in light area in wild-type animals, though both doses were without effect in mutant mice. Administration of buspirone (1 or 2 mg/kg) produced anxiolytic effects in wild-type mice. In contrast, only the highest dose of buspirone had anxiolytic results in mutant mice. Our findings reveal that CB 1 receptors are involved in the regulation of emotional responses, and play a pivotal role in the action mechanism of anxiolytics. They suggest that alterations in the functional activity of the CB 1 receptor may be related to the emergence of anxiety disorders, and may affect treatment with anxiolytics. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB 1 receptors

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Publisher
Elsevier
Copyright
Copyright © 2004 Elsevier Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/j.neuropharm.2004.01.003
pmid
15081793
Publisher site
See Article on Publisher Site

Abstract

The role of cannabinoid CB 1 receptors in the action of anxiolytics was examined. Deletion of CB 1 receptors resulted in increased anxiety-like behaviours in light/dark box, elevated plus maze and social interaction tests. Mutant mice presented basal low corticosterone concentrations and low proopiomelanocortin gene expression in the anterior lobe of the pituitary gland compared to wild-type mice. Ten minutes of restraint stress resulted in a twofold increase in corticosterone concentrations in the plasma of mutant mice, compared to wild-type mice. Bromazepam (50 or 100 μg/kg) markedly increased the time spent in light area in wild-type animals, though both doses were without effect in mutant mice. Administration of buspirone (1 or 2 mg/kg) produced anxiolytic effects in wild-type mice. In contrast, only the highest dose of buspirone had anxiolytic results in mutant mice. Our findings reveal that CB 1 receptors are involved in the regulation of emotional responses, and play a pivotal role in the action mechanism of anxiolytics. They suggest that alterations in the functional activity of the CB 1 receptor may be related to the emergence of anxiety disorders, and may affect treatment with anxiolytics.

Journal

NeuropharmacologyElsevier

Published: Jun 1, 2004

References

  • Age-related changes of anandamide metabolism in CB 1 cannabinoid receptor knockout mice: correlation with behaviour
    Maccarrone, M; Valverde, O; Barbaccia, M.L; Castane, A; Maldonado, R; Ledent, C; Parmentier, M; Finazzi-Agro, A

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