The role of D1-like dopamine receptors within the ventral tegmental area in the cannabidiol’s inhibitory effects on the methamphetamine-induced conditioned place preference in rats

Abstract

Cannabidiol (CBD) is a non-psychoactive drug extracted from marijuana. It is well established that CBD attenuates the reinforcing effects of drugs of abuse, although its mechanism of action is not fully understood. The current study tries to clarify the role of D1-like dopamine receptors (D1R) in the ventral tegmental area (VTA) in the inhibitory effects of the CBD on the acquisition and expression of methamphetamine (METH)-conditioned place preference (CPP). In the CPP training, adult male Wistar rats were conditioned with subcutaneous administration of METH (1 mg/kg) for five days. Three groups of animals were treated with multiple doses of SCH23390 (as a D1R antagonist; 0.25, 1, and 4 μg/0.3 μl saline) in the VTA, respectively, before intracerebroventricular (ICV) injection of CBD (10 μg/5 μl DMSO) in the acquisition phase. In the second experiment of the study, rats received SCH23390 in the VTA before ICV administration of CBD (50 μg/5 μl DMSO) in the expression of METH CPP. Here, the current study demonstrated that CBD inhibits the acquisition and expression of METH CPP, while microinjection of D1R antagonists (1 and 4 μg) into the VTA significantly reduced CBD’s suppressive effect on the acquisition and expression of METH place preference. Furthermore, this research demonstrated that either SCH23390 or CBD alone does not lead to place preference in the CPP paradigm. Based on these data, this study suggests that pharmacological manipulations of D1R may alter the CBD’s effect on METH-conditioned preference.