Cited by 197Cannabis and Cannabinoid ResearchTreatment of Major DepressionStress Responses and Cortisol

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Depression‐resistant endophenotype in mice overexpressing cannabinoid CB 2 receptors

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García‐Gutiérrez, MS, Pérez‐Ortiz, JM, Gutiérrez‐Adán, A, Manzanares, J·2010·British Journal of Pharmacology

DOI 10.1111/j.1476-5381.2010.00819.xPMC PMC2936848

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Abstract

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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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
ORCID: Gutiérrez‐Adán, A
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
DOI: 10.1111/j.1476-5381.2010.00819.x
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: public-domain
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
doi.wiley.com/10.1002/tdm_license_1.1 (tdm)
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 (medical) › Cannabis and Cannabinoid Research
Health Sciences › Medicine › Pharmacology (medical) › 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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Depression‐resistant endophenotype in mice overexpressing cannabinoid CB 2 receptors

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