Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward.
Daniela Braida, Valeria Limonta, Valeria Capurro, Paola Fadda, Tiziana Rubino, Paola Mascia, Alessia Zani, Enzo Gori, Walter Fratta, Daniela Parolaro, Mariaelvina Sala
Biological psychiatry February 1, 2008 Peer reviewed DOI: 10.1016/j.biopsych.2007.07.020 via PubMed
Summary
Salvinorin A, a kappa-opioid receptor agonist from Salvia divinorum, shows rewarding effects in Wistar rats at doses of 0.1 to 40 microg/kg for conditioned place preference and 0.1 to 0.5 microg/infusion for intracerebroventricular self-administration. Higher doses (160 microg/kg and 1 microg/infusion) were found to be aversive. The rewarding effect was blocked by the cannabinoid CB(1) antagonist rimonabant and the kappa-opioid antagonist nor-binaltorphimine, with dopamine levels increasing by about 150% in the nucleus accumbens after administration of 40 microg/kg.
Study at a glance
| Population | Wistar rats |
|---|---|
| Key finding | Salvinorin A produces rewarding effects in Wistar rats at specific doses while higher doses are aversive. |
Abstract
The recreational drug, Salvinorin A, derived from the plant of Salvia divinorum, is a potent and selective kappa-opioid receptor agonist. The abuse of selective k-agonists is a novel phenomenon, the mechanism of which is not fully understood. We investigated salvinorin A given SC on the conditioned place preference (.05-160 microg/kg) and intracerebroventricular (ICV) self-administration (.01-1 microg/infusion) paradigms, in Wistar rats. The present results demonstrate the rewarding effects of Salvinorin A in a range of doses between .1 and 40 microg/kg SC for conditioned place preference test and .1-.5 microg/infusion for ICV self-administration. Highest doses (160 microg/kg for conditioned place preference test and 1 microg/infusion for ICV self-administration) were aversive. The rewarding effect was antagonized by intraperitoneal (IP) pretreatment with the cannabinoid CB(1) 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 microg/kg SC), reaching a maximum value of about 150%. These data provide the demonstration of the rewarding effects of Salvinorin A through an interaction between kappa-opioid and (endo)cannabinoid system in rats.