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Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors

Urigüen, Leyre, Pérez-Rial, Sandra, Ledent, Catherine, Palomo, Tomás, Manzanares, Jorge·2004·Neuropharmacology

DOI 10.1016/j.neuropharm.2004.01.003

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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 microg/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.

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Authors: Urigüen, L., Pérez-Rial, S., Ledent, C., Palomo, T., & Manzanares, J.
Affiliations: Hospital Universitario 12 De Octubre (ES)
Université Libre de Bruxelles (BE)
Corresponding author: Manzanares, Jorge
ORCID: Urigüen, Leyre
Pérez-Rial, Sandra
Ledent, Catherine
Palomo, Tomás
Manzanares, Jorge
Venue: Neuropharmacology
Publisher: Elsevier BV
Published: 2004-06
Volume: 46
Issue: 7
Pages: 966-973
ISSN: 0028-3908 (ISSN-L)
DOI: 10.1016/j.neuropharm.2004.01.003
OpenAlex: W2031501939
Cited by: 218
References: 27
Citations by year: 2026: 3 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 4 · 2021: 8 · 2020: 4 · 2019: 7 · 2018: 9 · 2017: 8 · 2016: 7 · 2015: 16 · 2014: 8 · 2013: 14 · 2012: 9
FWCI: 9.84
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuropharmacology (publishedVersion)
PubMed (publishedVersion)
Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
Funders: Eusko Jaurlaritza
National Institutes of Health
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: CB1 receptor, anxiolytics, anxiety-like behavior, bromazepam, buspirone, corticosterone, proopiomelanocortin, pituitary gland, restraint stress, CB1 receptor knockout mice, emotion regulation, anxiety disorders
MeSH terms: Animals, Anxiety, Darkness, Lighting, Male, Motor Activity, Anti-Anxiety Agents, Mice, Knockout, Receptor, Cannabinoid, CB1, Mice

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Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors

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