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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1522210

The effect of cannabinoid type Ⅱ receptor on the excitability of substantia nigra dopaminergic neurons

Provisionally accepted
Sha Zhao Sha Zhao ShunFeng Liu ShunFeng Liu Yongxin Gong Yongxin Gong ZeGang Ma ZeGang Ma *
  • College of Basic Medicine, Qingdao University, Qingdao, Shandong Province, China

The final, formatted version of the article will be published soon.

    The biological effects of cannabinoids are mainly mediated by two members of the G-protein-coupled-receptor family: cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R). Unlike CB1R, CB2R is considered a "peripheral" cannabinoid receptor. However, recent studies have found that CB2R is widely expressed in the central nervous system and is involved in dopamine related behavioral regulation, including dietary behavior, weight regulation, anxiety, and schizophrenia like behavior. Our previous laboratory research demonstrated that activating CB2R on dopaminergic neurons in the ventral tegmental area can regulate addictive behavior in animals by inhibiting neuronal excitability. However, it is currently unclear whether CB2R on dopaminergic neurons in the substantia nigra compacta (SNc) has similar therapeutic potential. Brain patch clamp results have shown that the CB2R agonist JWH133 significantly inhibits the discharge of SNc dopamine neurons in a concentration dependent manner. The pharmacological blocker AM630 of CB2R can reverse this inhibitory effect, indicating that the expression of CB2R in SNc dopaminergic neurons is functional. After treatment with JWH133, the number of induced action potentials decreased, and the peak potential interval time, action potential start time, and potential amplitude after hyperpolarization amplitude all increased. In addition, synaptic current results showed that JWH133 can significantly reduce the frequency of miniature excitatory postsynaptic currents, indicating that activating CB2R to some extent inhibits the release of presynaptic glutamate and indirectly excites postsynaptic neurons.

    Keywords: Cannabinoid type II receptor, JWH133, AM630, Substantial nigra, dopamine neurons, Firing activity

    Received: 04 Nov 2024; Accepted: 28 Jan 2025.

    Copyright: © 2025 Zhao, Liu, Gong and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: ZeGang Ma, College of Basic Medicine, Qingdao University, Qingdao, 266071, Shandong Province, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.