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Depression-resistant endophenotype in mice overexpressing cannabinoid CB(2) receptors
M S García-Gutiérrez1, J M Pérez-Ortiz, A Gutiérrez-Adán
1Instituto de Neurociencias, Campus de San Juan, Universidad Miguel Hernández-CSIC, San Juan de Alicante, Alicante, Spain.
British Journal of Pharmacology
|July 24, 2010
Summary
Increased CB(2) receptor expression reduced depressive behaviors in mice. This suggests the CB(2) receptor is a potential therapeutic target for depressive disorders.
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- The role of cannabinoid receptor 2 (CB2) in regulating mood disorders is under investigation.
- Understanding CB2 receptor function is crucial for developing novel depression treatments.
Purpose of the Study:
- To evaluate the function of CB2 receptors in modulating depressive-like behaviors.
- To assess the therapeutic potential of targeting CB2 receptors for depression.
Main Methods:
- Utilized transgenic mice overexpressing CB2 receptors (CB2xP) and wild-type (WT) mice.
- Employed behavioral tests including Tail Suspension Test (TST), Novelty-Suppressed Feeding Test (NSFT), and Chronic Mild Stress (CMS).
- Analyzed CB2 receptor and Brain-Derived Neurotrophic Factor (BDNF) gene and protein expression.
Main Results:
- CB2 receptor overexpression decreased depressive-like behaviors in TST and NSFT.
- CMS did not affect TST or sucrose consumption in CB2xP mice, with no changes in BDNF expression.
- CB2 receptor antagonist AM630 showed antidepressant-like effects in WT mice but not CB2xP mice, and chronic AM630 treatment mitigated CMS effects in WT mice.
Conclusions:
- Elevated CB2 receptor expression significantly alleviates depressive behaviors.
- The CB2 receptor presents a promising therapeutic target for depressive disorders.
