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 via PubMed
Summary
AI-generated from the abstractSalvinorin A, a drug from the plant Salvia divinorum, produces rewarding effects in rats at low to moderate doses but becomes aversive at the highest doses tested. In conditioned place preference tests, doses between 0.1 and 40 micrograms per kilogram given subcutaneously were rewarding, while 160 micrograms per kilogram was aversive. In self-administration tests, doses of 0.1 to 0.5 micrograms per infusion given intracerebroventricularly were rewarding, but 1 microgram per infusion was aversive. The rewarding effect was blocked by pretreatment with either a cannabinoid CB1 receptor antagonist or a kappa-opioid receptor antagonist. Salvinorin A also increased dopamine levels in the shell of the nucleus accumbens by about 150 percent. These findings indicate that the rewarding effects involve interaction between kappa-opioid and endocannabinoid systems.
Study at a glance
| 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 |
| Citations | 107 |
| Key finding | 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.