Involvement of κ-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

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)286-292
Number of pages7
JournalBiological Psychiatry
Issue number3
Publication statusPublished - Feb 1 2008


  • κ-opioid receptor
  • Conditioned place preference
  • dopamine
  • microdialysis
  • self-administration
  • SR 141716A

ASJC Scopus subject areas

  • Biological Psychiatry


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