Involvement of kappa-Opioid and Endocannabinoid System on Salvinorin A-Induced Reward

Background: The recreational drug, Salvinorin A, derived from the plant of Salvia divinorum, is a potent and selective K-Opioid receptor agonist. The abuse of selective k-agonists is a novel phenomenon, the mechanism of which is not fully understood. Methods: We investigated salvinorin A given SC on the conditioned place preference (.05-160 mu g/kg) and intracerebroventricular (ICV) self-administration (.01-1 mu g/infusion) paradigms, in Wistar rats. Results: The present results demonstrate the rewarding effects of Salvinorin A in a range of doses between .1 and 40 mu g/kg SC for conditioned place preference test and .1-5 mu g/infusion for ICV self-administration. Highest doses (160 mu g/kg for conditioned place preference test and I mu g/infusion for ICV self-administration) were aversive. The rewarding effect was antagonized by intraperitoneal (IP) pretreatment with the cannabinoid CB1 receptor antagonist, rimonabant [N-piperidino-5-(4-chlorophenyl) 1-(2,4-dichloro phenyl)-4 methyl pyrazole 3-carboxamide] (1 mg/kg), and the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) (10 mg/kg). In the shell of nucleus accumbens, dopamine extracellular levels were increased after administration of salvinorin A (40 mu g/kg SC), reaching a maximum value of about 150%. Conclusions: These data provide the demonstration of the rewarding effects of Salvinorin A through an interaction between kappa-Opioid and (endo)cannabinoid system in rats.