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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1496657

Role for Rab10 in cocaine-induced behavioral effects is associated with GABAB receptors membrane expression in the nucleus accumbens

Provisionally accepted
Zhuoxuan Yu Zhuoxuan Yu 1Qiang Fu Qiang Fu 2Tianyun Qiu Tianyun Qiu 3Caidi Yang Caidi Yang 1Mingfen Lu Mingfen Lu 4Qinghua Peng Qinghua Peng 5Jianhua Yang Jianhua Yang 4Zhenzhen Hu Zhenzhen Hu 4*
  • 1 The First Clinical Medical College, Nanchang University, Nanchang, China
  • 2 Department of Respiration, Department Two, Jiangxi Provincial People's Hospital, Nanchang, Jiangxi Province, China
  • 3 Department of Clinical Laboratory, Hankou Hospital, Wuhan, Hebei, China
  • 4 School of Basic Medical Sciences, Nanchang University, Nanchang, China
  • 5 Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China

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

    Aims: Previous studies have demonstrated that Ras-related GTP-binding protein Rab10 (Rab10) participates in psychostimulant-induced behavioral effects. Here, we showed that Rab10 in the nucleus accumbens (NAc) of male animals affects the development of cocaine-induced behavioral effects, which are associated with the plasma membrane expression of GABAB heteroreceptor (GABABR). Methods: We performed flow cytometry, immunoendocytosis, pHluorin activity analysis, electrophysiology analysis, and open field test to explore the role of Rab10 in modulating the membrane expression and function of GABABR, as well as its regulatory effect on cocaine-induced behavioral effects. Results: Transcriptomics analysis showed that Rab10 was elevated by acute cocaine treatment. Membrane levels of Rab10 increased within day 1 of the cocaine treatment, subsequently decreased in following timepoints. Rab10 deficiency in NAc regions significantly increased cocaine-inhibited membrane GABABR levels and inhibited cocaine-induced hyperlocomotion and behavioral sensitization. In addition, GAD67+ neurons from NAc regions treated with cocaine revealed significantly decreased Rab10 membrane expression. Furthermore, NAc neurons-specific Rab10 knockout resulted in a significant increase in the cocaine-inhibited membrane expression of GABABR, together with increases in mIPSCs amplitude and attenuation of baclofen-amplified Ca2+ influx. Conclusion: These results uncover a new mechanism by which Rab10-GABABR signaling can be a potential mechanism for regulating cocaine-induced behavioral effects.

    Keywords: Cocaine, Nucleus accumbens (NAc), behavioral sensitization, ras-related GTPbinding protein Rab10 (Rab10), gamma aminobutyric acid type B receptor (GABA B R)

    Received: 15 Sep 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Yu, Fu, Qiu, Yang, Lu, Peng, Yang and Hu. 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: Zhenzhen Hu, School of Basic Medical Sciences, Nanchang University, Nanchang, China

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