Intra-Accumbal D1-But not D2-Like Dopamine Receptor Antagonism Reverses the Inhibitory Effects of Cannabidiol on Extinction and Reinstatement of Methamphetamine Seeking Behavior in Rats

Introduction: Methamphetamine (METH) is an addictive psychostimulant that facilitates dopamine transmission to the nucleus accumbens (NAc), resulting in alterations in the mesocorticolimbic brain regions. Cannabidiol (CBD) is considered the second most abundant component of cannabis and is believed to decrease the METH effects. Reversing psychostimulant-induced abnormalities in the mesolimbic dopamine system is the main mechanism for this effect. Various other mechanisms have been proposed: increasing endocannabinoid system activity and modulating gamma-aminobutyric acid (GABA) and glutamate neurons in NAc. However, the exact CBD action mechanisms in reducing drug addiction and relapse vulnerability remain unclear.Methods and Results: The present study aimed to investigate the effects of intracerebroventricular (ICV) administrating 5, 10, and 50 mu g/5 mu L CBD solutions on the extinction period and reinstatement phase of a METH-induced conditioned place preference. This research also aimed to examine the NAc D1-like dopamine receptor (D1R) and D2-like dopamine receptor (D2R) roles in the effects of CBD on these phases, as mentioned earlier, using SCH23390 and sulpiride microinjections as an antagonist of D1R and D2R. The obtained results showed that microinjection of CBD (10 and 50 mu g/5 mu L, ICV) suppressed the METH-induced reinstatement and significantly decreased mean extinction latency in treated groups compared to both vehicles and/or untreated control groups. In addition, the results demonstrated that administrating intra-accumbal SCH23390 (1 and 4 mu g/0.5 mu L saline) reversed the inhibitory effects of CBD on extinction and reinstatement phases while different doses of sulpiride (0.25, 1, and 4 mu g/0.5 mu L; dimethyl sulfoxide 12%) could not alter the CBD effects.Conclusions: In summary, this study showed that CBD made shorter extinction latencies and suppressed the METH reinstatement, in part, by interacting with D1R but not D2R in the NAc.

Automated summary

This study found that CBD can reduce METH reinstatement and shorten extinction latency, in part, by interacting with D1R in the NAc.