Cannabidiol Plays a Modulatory Function on the Methamphetamine-Induced Reward Through Hippocampal D2-Like Dopamine Receptors

Methamphetamine (METH), a stimulant that is extremely addictive, directly affects the central nervous system. METH’s abuse and consumption are directly linked to mental illnesses, psychosis, and behavioral and cognitive impairments. It may disrupt the reward system and dopaminergic transmission. METH’s rewarding qualities are associated with a rise in dopamine. Additionally, cannabidiol (CBD), one of the primary cannabinoid components of the cannabis plant, significantly affects dopaminergic transmission and may aid in reward- and addiction-related behaviors. To shed light on the role of the D2-like dopamine receptor (D2R) in the hippocampal dentate gyrus (DG), the present study examined the effects of CBD on the acquisition and expression of the conditioned place preference (CPP) induced by METH. The function of D2R was ascertained by delivering Sulpiride microinjections, as a D2R antagonist Sulpiride (0.25, 1, and 4 μg/0.5 μL DMSO12%) into the DG. Moreover, an intracerebroventricular injection of CBD at a dose of 10 μg/5 μL for CPP acquisition and 50 μg/5 μL for CPP expression was given to rats. According to the current research, CBD dramatically reduced the acquisition and expression of CPP resulting from METH. However, Sulpiride suppressed the effect of CBD on METH-induced CPP acquisition and expression, with a greater impact on expression experiments. Ultimately, this study proposed that the expression experiment of METH-induced CPP appears to be heavily dependent on D2R in the DG.