Context‐dependent effects of CB1 cannabinoid gene disruption on anxiety‐like and social behaviour in mice
Abstract
Contrasting data were reported regarding the effects of cannabinoids on anxiety and social behaviour in both animals and humans. The cognitive effects of cannabinoids and their interactions with the HPA‐axis raise the possibility that cannabinoid effects are context but not behaviour specific. To assess this hypothesis, we submitted CB1 receptor knock‐out (CB1‐KO) and wild‐type (WT) mice to tests, which involved similar behaviours, but the behavioural context was different. The elevated plus‐maze test was performed under less and more anxiogenic conditions, i.e. under low and high light, respectively. We also compared the social behaviour of the two genotypes in the resident/intruder and social interaction tests. Both tests represent a social challenge and induce similar behaviours, but involve different contexts. The behaviour of CB1‐KO and WT mice was similar under low light, but CB1 gene disruption increased anxiety‐like behaviour under the high light condition. CB1 gene disruption promoted aggressive behaviour in the home‐cage, whereas it inhibited social behaviour in the unfamiliar cage. Thus, the anxiogenic‐like effect was restricted to the more stressful unfamiliar environment. These data suggest that the effects of CB1 gene disruption were context and not behaviour specific. Novelty stress resulted in higher ACTH levels in CB1‐KOs than in WTs, which suggests that context dependency occurred in conjunction with an altered HPA axis function. The present data at least partly explain contrasting effects of cannabinoids in different contexts as well as in different species and strains that show differential stress responses and coping strategies.
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Genetic removal of CB1 receptors alters social interactions in mice in a context-dependent manner.
“Genetic removal of CB1 receptors alters social interactions in mice in a context-dependent manner,32 which may be related to social anxiety and/or cognition.37,38”
From Enhancement of anandamide-mediated endocannabinoid signaling corrects autism-related social impairment (2016) · cites this paper as [32]
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- Authors
- Haller, J., Varga, B., Ledent, C., Barna, I., & Freund, T. F.
- Affiliations
- HUN-REN Institute of Experimental Medicine (HU)
- Université Libre de Bruxelles (BE)
- Corresponding author
- Haller, J.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2004-04
- Volume
- 19
- Issue
- 7
- Pages
- 1906-1912
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W2168003262
- Cited by
- 284
- References
- 52
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 6 · 2023: 14 · 2022: 8 · 2021: 10 · 2020: 8 · 2019: 7 · 2018: 7 · 2017: 18 · 2016: 13 · 2015: 19 · 2014: 13 · 2013: 16 · 2012: 12
- FWCI
- 8.99
- 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)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- CB1 receptor, anxiety-like behavior, social behavior, context sensitivity, hypothalamic-pituitary-adrenal axis, ACTH, novelty stress, elevated plus maze, resident-intruder test, aggression, stress response
- MeSH terms
- Adrenocorticotropic Hormone, Animals, Anxiety, Behavior, Animal, Exploratory Behavior, Interpersonal Relations, Light, Locomotion, Social Behavior, Time Factors, Mice, Knockout, Maze Learning, Receptor, Cannabinoid, CB1, Mice
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