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 inhibitory responses in the cellular protein abundance of Sigma1R, p-AKT, p-GSK3β, and p-CREB across various brain regions. The present study found that METH can induce CPP in rats. When a pretreatment of CBD is applied, the CBD can weaken CPP in METH-induced rats by regulating the SigmaR1/AKT/GSK-3β/CREB signaling pathway. The results of this study indicate that CBD has a potential therapeutic effect on METH-induced rewarding effects.

中文翻译：

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卡那比二醇通过Sigma1R / AKT /GSK-3β/ CREB信号传导通路减弱了甲基苯丙胺诱导的条件位置偏好。

甲基苯丙胺（METH）是一种高度成瘾的精神刺激药。Cannabidiol（CBD）是一种没有精神刺激活性的外源性大麻素，对阿片类药物成瘾具有潜在的治疗作用。然而，尚不清楚CBD是否对METH诱导的动机有治疗作用。本研究通过调节Sigma1R和AKT-GSK3β-CREB信号通路来研究CBD是否对METH诱导的条件性位置偏爱（CPP）具有保护作用。将70只大鼠平均随机分为7组。通过2 mg / kg METH的腹膜内注射（IP）建立大鼠CPP模型。接下来，在注射盐水或METH之前1小时进行腹膜内注射10、20、40和80 mg / kg CBD。Sigma1R，AKT，p-AKT，GSK-3β，p-GSK-3β，CREB，用western blot分析法检测大鼠前额叶皮层，伏隔核，海马和腹侧被盖肌中的p-CREB和p-CREB。发现CBD以剂量依赖性方式抑制METH诱导的CPP。在METH诱导的CPP模型中，Sigma1R，p-AKT，p-GSK3β和p-CREB的表达水平显着增加。涉及不同剂量CBD的治疗在整个大脑区域的Sigma1R，p-AKT，p-GSK3β和p-CREB的细胞蛋白质丰度中引起了不同的抑制反应。本研究发现，甲乙二胺可诱导大鼠CPP。当应用CBD预处理时，CBD可以通过调节SigmaR1 / AKT /GSK-3β/ CREB信号通路来减弱METH诱导的大鼠的CPP。这项研究的结果表明，CBD对METH诱导的奖励作用具有潜在的治疗作用。