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 DOI: 10.1016/j.biopsych.2007.07.020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Wistar rats |
| Interventions | Salvinorin A rimonabant nor-binaltorphimine |
| Dose | 0.05-160 microg/kg SC for conditioned place preference; 0.01-1 microg/infusion for ICV self-administration; rimonabant 1 mg/kg IP; nor-BNI 10 mg/kg IP |
| Topics | Salvia divinorum |
| Citations | 107 |
| Key findings | Salvinorin A has rewarding effects at low to moderate doses and aversive effects at high doses, mediated by kappa-opioid and cannabinoid CB1 receptor systems. |
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.