The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety
Abstract
The aim of this study was to compare the effects of the genetic and pharmacological disruption of CB1 cannabinoid receptors on the elevated plus‐maze test of anxiety. In the first experiment, the behaviour of CB1‐knockout mice and wild‐type mice was compared. In the second experiment, the cannabinoid antagonist SR141716A (0, 1, and 3 mg/kg) was administered to both CB1‐knockout and wild type mice. Untreated CB1‐knockout mice showed a reduced exploration of the open arms of the plus‐maze apparatus, thus appearing more anxious than the wild‐type animals, however no changes in locomotion were noticed. The vehicle‐injected CB1‐knockout mice from the second experiment also showed increased anxiety as compared with wild types. Surprisingly, the cannabinoid antagonist SR141716A reduced anxiety in both wild type and CB1 knockout mice. Locomotor behaviour was only marginally affected. Recent evidence suggests the existence of a novel cannabinoid receptor in the brain. It has also been shown that SR141716A binds to both the CB1 and the putative novel receptor. The data presented here supports these findings, as the cannabinoid receptor antagonist affected anxiety in both wild type and CB1‐knockout mice. Tentatively, it may be suggested that the discrepancy between the effects of the genetic and pharmacological blockade of the CB1 receptor suggests that the novel receptor plays a role in anxiety.
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These CB1 receptor adaptations give rise to an anxious/depressive phenotype.
“which in turn give rise to an anxious/depressive phenotype20, 21.”
From Elevated brain cannabinoid CB1 receptor availability in post-traumatic stress disorder: A positron emission tomography study (2013) · cites this paper as [20]
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- Authors
- Haller, J., Bakos, N., Szirmay, M., Ledent, C., & Freund, T. F.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Université Libre de Bruxelles (BE)
- Corresponding author
- Freund, T. F.
- ORCID
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2002-10
- Volume
- 16
- Issue
- 7
- Pages
- 1395-1398
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2027352187
- Cited by
- 354
- References
- 26
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 5 · 2023: 14 · 2022: 6 · 2021: 14 · 2020: 9 · 2019: 8 · 2018: 11 · 2017: 13 · 2016: 11 · 2015: 16 · 2014: 16 · 2013: 18 · 2012: 18
- FWCI
- 9.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- Hungarian Scientific Research Fund
- National Institute of Mental Health (R01MH054671, MH54671)
- 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, anxiety, CB1 knockout mice, SR141716A, cannabinoid receptor antagonists, elevated plus maze, locomotor behaviour
- MeSH terms
- Rimonabant, Animals, Anxiety, Exploratory Behavior, Motor Activity, Piperidines, Pyrazoles, Receptors, Drug, Mice, Knockout, Maze Learning, Receptors, Cannabinoid, Mice
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