Involvement of κ-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 κ-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 μg/kg) and intracerebroventricular (ICV) self-administration (.01–1 μg/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 μg/kg SC for conditioned place preference test and .1–.5 μg/infusion for ICV self-administration. Highest doses (160 μg/kg for conditioned place preference test and 1 μg/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 κ-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 μg/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 κ-opioid and (endo)cannabinoid system in rats.