10.6084/M9.FIGSHARE.20379579.V1
Liu Liu
Liu
Liu
Juan Li
Juan
Li
Chan Wang
Chan
Wang
Yue Xu
Yue
Xu
Chi-Kwan Leung
Chi-Kwan
Leung
Genmeng Yang
Genmeng
Yang
Shucheng Lin
Shucheng
Lin
Shuwei Zhang
Shuwei
Zhang
Yi Tan
Yi
Tan
Huijie Zhang
Huijie
Zhang
Haowei Wang
Haowei
Wang
Jianxing Liu
Jianxing
Liu
Ming Li
Ming
Li
Xiaofeng Zeng
Xiaofeng
Zeng
Cannabidiol attenuates methamphetamine-induced conditioned place preference in male rats and viability in PC12 cells through the Sigma1R/AKT/GSK3β/CREB signaling pathway
<p><i>Background:</i> 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.</p> <p><i>Objectives:</i> To investigate the effects of cannabidiol on methamphetamine-induced conditioned place preference (CPP) and the viability of PC12 cells.</p> <p><i>Methods:</i> 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.</p> <p><i>Results:</i> 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).</p> <p><i>Conclusions:</i> 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.</p>
Biochemistry
Genetics
Molecular Biology
Neuroscience
Pharmacology
Chemical Sciences not elsewhere classified
Mental Health
Taylor & Francis
2022
2022-07-26
2024-02-28
Dataset
1719878 Bytes
10.6084/m9.figshare.20379579
10.1080/00952990.2022.2073450
CC BY 4.0