Depression‐resistant endophenotype in mice overexpressing cannabinoid CB 2 receptors
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Background and purpose: The present study evaluated the role of CB 2 receptors in the regulation of depressive‐like behaviours. Transgenic mice overexpressing the CB 2 receptor (CB2xP) were challenged with different types of acute and chronic experimental paradigms to evaluate their response in terms of depressive‐like behaviours. Experimental approach: Tail suspension test (TST), novelty‐suppressed feeding test (NSFT) and unpredictable chronic mild stress tests (CMS) were carried out in CB2xP mice. Furthermore, acute and chronic antidepressant‐like effects of the CB 2 receptor‐antagonist AM630 were evaluated by means of the forced swimming test (FST) and CMS, respectively, in wild‐type (WT) and CB2xP mice. CB 2 gene expression, brain‐derived neurotrophic factor (BDNF) gene and protein expressions were studied in mice exposed to CMS by real‐time PCR and immunohistochemistry, respectively. Key results: Overexpression of CB 2 receptors resulted in decreased depressive‐like behaviours in the TST and NSFT. CMS failed to alter the TST and sucrose consumption in CB2xP mice. In addition, no changes in BDNF gene and protein expression were observed in stressed CB2xP mice. Interestingly, acute administration of AM630 (1 and 3 mg·kg −1 , i.p.) exerted antidepressant‐like effects on the FST in WT, but not in CB2xP mice. Chronic administration of AM630 for 4 weeks (1 mg·kg −1 ; twice daily, i.p.) blocked the effects of CMS on TST, sucrose intake, CB 2 receptor gene, BDNF gene and protein expression in WT mice. Conclusion and implications: Taken together, these results suggest that increased CB 2 receptor expression significantly reduced depressive‐related behaviours and that the CB 2 receptor could be a new potential therapeutic target for depressive‐related disorders.
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Mice over-expressing CB2 have reduced vulnerability to chronic unpredictable stress and depression-like behaviors at baseline.
“Mice over-expressing CB2 have reduced vulnerability to CUS and depression-like behaviors at baseline [41, 42]”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [41]
Ectopic genetic overexpression of CB2R in mice may mitigate behavioral reactions to chronic stress.
“ectopic genetic overexpression CB2R in mice (Racz et al., 2008) may mitigate behavioral reactions to chronic stress (Garcia-Gutierrez et al., 2010).”
From The endocannabinoid system as a target for novel anxiolytic drugs (2017) · cites this paper as Garcia-Gutierrez et al., 2010
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- Authors
- García‐Gutiérrez, M., Pérez‐Ortiz, J., Gutiérrez‐Adán, A., & Manzanares, J.
- Affiliations
- Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (ES)
- Instituto de Neurociencias (ES)
- Corresponding author
- Manzanares, J
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2010-04-26
- Volume
- 160
- Issue
- 7
- Pages
- 1773-1784
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2936848
- OpenAlex
- W2054653962
- Cited by
- 196
- References
- 69
- Citations by year
- 2026: 6 · 2025: 13 · 2024: 6 · 2023: 13 · 2022: 20 · 2021: 19 · 2020: 9 · 2019: 12 · 2018: 14 · 2017: 11 · 2016: 8 · 2015: 10 · 2014: 13 · 2013: 11 · 2012: 15
- FWCI
- 10.09
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- British Journal of Pharmacology (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
- Funders
- Ministerio de Ciencia e Innovación (RETICS RD06/0001/1004, SAF 2008-01106)
- Plan Nacional sobre Drogas
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- CB2 receptor, depression, depression-like behavior, AM630, antidepressant-like effects, chronic unpredictable mild stress, brain-derived neurotrophic factor, endophenotypes, tail suspension test, forced swim test, therapeutic target
- MeSH terms
- Animals, Antidepressive Agents, Anxiety, Behavior, Animal, Depression, Disease Models, Animal, Feeding Behavior, Hippocampus, Immunohistochemistry, Indoles, Male, Mice, Inbred ICR, Mice, Transgenic, Restraint, Physical, Stress, Psychological, Swimming, Gene Expression, Brain-Derived Neurotrophic Factor, Receptor, Cannabinoid, CB2, Mice
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