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Cannabidiol attenuates methamphetamine-induced conditioned place preference in male rats and viability in PC12 cells through the Sigma1R/AKT/GSK3β/CREB signaling pathway.

Authors :
Liu, Liu
Li, Juan
Wang, Chan
Xu, Yue
Leung, Chi-Kwan
Yang, Genmeng
Lin, Shucheng
Zhang, Shuwei
Tan, Yi
Zhang, Huijie
Wang, Haowei
Liu, Jianxing
Li, Ming
Zeng, Xiaofeng
Source :
American Journal of Drug & Alcohol Abuse. 2022, Vol. 48 Issue 5, p548-561. 14p.
Publication Year :
2022

Abstract

Background: Methamphetamine use is associated with several negative consequences, including neurotoxicity and greater probability of exhibiting a substance use disorder. Sigma1 receptor is involved in the neurobiological basis of several drug use disorders. Cannabidiol has received attention in the treatment of drug use disorders and neurotoxicity.Objectives: To investigate the effects of cannabidiol on methamphetamine-induced conditioned place preference (CPP) and the viability of PC12 cells.Methods: Adult male rats (n = 70) underwent methamphetamine (2 mg/kg, IP) induced CPP, and were administered cannabidiol (10, 20, 40, or 80 mg/kg, IP) during the methamphetamine withdrawal period for five consecutive days. Methamphetamine (0.5 mg/kg) was then injected to reactivate CPP. Four brain regions (ventral tegmental area, nucleus accumbens, prefrontal cortex, and hippocampus) were extracted after the last test. PC12 cells were treated with cannabidiol, Sigma1R-siRNA, or BD1047 before methamphetamine exposure.Results: Administration of 20, 40, or 80 mg/kg cannabidiol facilitated CPP extinction (80 mg/kg, p < .001) and prevented CPP development (80 mg/kg, p < .0001). This was associated with changes in the expression of Sigma1R (ventral tegmental area, 80 mg/kg, p < .0001) in the four brain regions. Cannabidiol protected the PC12 cell's viability (10 μM, p = .0008) and inhibited the methamphetamine-induced activation of the AKT/GSK3β/CREB signaling pathway by mediating Sigma1R (10 μM, p < .0001).Conclusions: Cannabidiol seems to inhibit the rewarding effects of methamphetamine and the effects of this drug on cell viability. Sigma1R should be given further consideration as a potential target for cannabidiol. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00952990
Volume :
48
Issue :
5
Database :
Academic Search Index
Journal :
American Journal of Drug & Alcohol Abuse
Publication Type :
Academic Journal
Accession number :
159632832
Full Text :
https://doi.org/10.1080/00952990.2022.2073450