Impaired action of anxiolytic drugs in mice deficient in cannabinoid CB1 receptors
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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Diazepam increases AEA in the amygdala.
“the anxiolytic agent, diazepam, increases AEA in the amygdala, and bromazepam and buspirone have diminished anxiolytic effects in CB1knockout mice (Micale et al, 2009;Uriguen et al, 2004).”
From Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans (2012) · cites this paper as Uriguen et al, 2004
Bromazepam and buspirone have diminished anxiolytic effects in CB1-knockout mice.
“the anxiolytic agent, diazepam, increases AEA in the amygdala, and bromazepam and buspirone have diminished anxiolytic effects in CB1knockout mice (Micale et al, 2009;Uriguen et al, 2004).”
From Acute stress increases circulating anandamide and other N-acylethanolamines in healthy humans (2012) · cites this paper as Uriguen et al, 2004
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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
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2004-06
- Volume
- 46
- Issue
- 7
- Pages
- 966-973
- ISSN
- 0028-3908 (ISSN-L)
- 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
- 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 › 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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