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Cannabinoid type 2 receptors play a crucial role in social defeat-induced depression.

Author information

Affiliations

  • 1. Department of Physiology, Laboratory of Neurodegenerative Diseases, Changzhi Medical College, Changzhi, Shanxi 046000, China; Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
      Authors
    • Chen XR 1
    (1 author)
  • 2. Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China.
      Authors
    • Yu R 2
    • Wang J 2
    • Huang HJ 2
    • Li HY 2
    • Wu GC 2
    (5 authors)
  • 3. Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Lane 826, Zhangheng Road, Shanghai 201203, China.
      Authors
    • Chen J 3
    (1 author)
  • 4. Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai University of Medicine & Health Sciences, Shanghai 201318, China.
      Authors
    • Han QQ 4
    (1 author)
  • 5. Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, State Key Laboratory of Medical Neurobiology, Institutes of Brain Science, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Key Laboratory of Acupuncture Mechanism and Acupoint Function, Fudan University, Shanghai 200433, China.
      Authors
    • Yu J 5
    (1 author)

ORCIDs linked to this article

Journal of Affective Disorders, 01 Jan 2024, 348:333-344
https://doi.org/10.1016/j.jad.2023.12.089 PMID: 38171418 

Abstract 

Background

The endocannabinoid system plays a crucial role in regulating mood, but the specific involvement of cannabinoid receptor type 2 (CB2R) in depression remains poorly understood. Similarly, the mechanisms by which electroacupuncture (EA) provides therapeutic benefits for depression are not clearly defined. This research aims to explore the function of CB2R in depression and examine if the therapeutic effects of EA are associated with the hippocampal CB2R system.

Methods

Mice experiencing social defeat stress (SDS) were used to model depression and anxiety behaviors. We quantified hippocampal CB2R and N-arachidonoylethanolamide (AEA) levels. The efficacy of a CB2R agonist, JWH133, in mitigating SDS-induced behaviors was evaluated. Additionally, EA's impact on CB2R and AEA was assessed, along with the influence of CB2R antagonist AM630 on EA's antidepressant effects.

Results

SDS led to depressive and anxiety-like behaviors, with corresponding decreases in hippocampal CB2R and AEA. Treatment with JWH133 ameliorated these behaviors. EA treatment resulted in increased CB2R and AEA levels, while AM630 blocked these antidepressant effects.

Limitations

The study mainly focused on the SDS model, which may not entirely reflect other depression models. Besides, further investigation is needed to understand the precise mechanisms by which CB2R and AEA contribute to EA's effects.

Conclusions

The study suggests hippocampal downregulation of CB2R and AEA contributes to depression. Upregulation of CB2R and AEA in response to EA suggests their involvement in EA's antidepressant effects. These findings provide insights into the role of the hippocampal CB2R system in depression and the potential mechanisms underlying EA's therapeutic effects.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.jad.2023.12.089

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