GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal

Jinlong Zhang; Jie Yan; Shuyue Li; Qianqian Chen; Jiang Lin; Yilin Peng; Yuhang Liu; Binbin Wang; Xinrong Wei; Chen Sun; Shuliang Niu

doi:10.1016/j.heliyon.2024.e30462

GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal

Heliyon. 2024 Apr 27;10(9):e30462. doi: 10.1016/j.heliyon.2024.e30462. eCollection 2024 May 15.

Authors

Jinlong Zhang^{1

2}, Jie Yan^{1

2}, Shuyue Li¹, Qianqian Chen², Jiang Lin², Yilin Peng², Yuhang Liu², Binbin Wang², Xinrong Wei¹, Chen Sun³, Shuliang Niu^{1

4}

Affiliations

¹ Department of Forensic Science, School of Basic Medical Science, Xinjiang Medical University, Urumqi, 830011, China.
² Department of Forensic Science, School of Basic Medical Science, Central South University, Changsha, 410000, China.
³ School of Public Health, Xinjiang Medical University, Urumqi, 830011, China.
⁴ Department of Human Anatomy, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, 830011, China.

Abstract

Methamphetamine is a potent and highly addictive neurotoxic psychostimulant that triggers a spectrum of adverse emotional responses during withdrawal. G-protein coupled receptor 55 (GPR55), a novel endocannabinoid receptor, is closely associated with mood regulation. Herein, we developed a murine model of methamphetamine-induced anxiety- and depressive-like behavior during abstinence which showed a decreased GPR55 expression in the hippocampus. Activation of GPR55 mitigated these behavioral symptoms, concomitantly ameliorating impairments in hippocampal neurogenesis and reducing neuroinflammation. These findings underscore the pivotal role of GPR55 in mediating the neuropsychological consequences of methamphetamine withdrawal, potentially via mechanisms involving the modulation of hippocampal neurogenesis and inflammation.

Keywords: Anxiety; Depression; GPR55; Methamphetamine.