Cannabidiol attenuates methamphetamine-induced conditioned place preference via the Sigma1R/AKT/GSK-3β/CREB signaling pathway in rats.

Toxicology Research
Genmeng YangDongxian Zhang

Abstract

Methamphetamine (METH) is a highly addictive psychostimulant. Cannabidiol (CBD) is an exogenous cannabinoid without psychostimulating activity, which has potential therapeutic effects on opioid addiction. However, it is unclear whether CBD has therapeutic effects on METH-induced motivational effects. The present study examines whether CBD has a protective effect on METH-induced conditioned place preference (CPP) in rats by regulating the Sigma1R and AKT-GSK3β-CREB signaling pathway. Seventy rats were equally and randomly divided into seven groups. The rat CPP model was established via the intraperitoneal injection (IP) of 2 mg/kg of METH. Next, the intraperitoneal injection of 10, 20, 40, and 80 mg/kg CBD was performed 1 h prior to the injection of saline or METH. The protein expression levels of Sigma1R, AKT, p-AKT, GSK-3β, p-GSK-3β, CREB, and p-CREB in the rats' prefrontal cortex, nucleus accumbens, and hippocampus and ventral tegmental were detected using western blot analysis. CBD was found to inhibit METH-induced CPP in a dose-dependent fashion. The expression levels of Sigma1R, p-AKT, p-GSK3β, and p-CREB increased significantly in the METH-induced CPP model. Treatment involving different doses of CBD caused differential i...Continue Reading

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