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.
Comparable studies
Other preclinical and animal studies on salvia divinorum, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Mice | 2005 | Experimental study | |
| Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents Male Sprague-Dawley rats and male Albino Swiss mice | 2009 | Experimental study | |
| Role of kappa-opioid receptors in the effects of salvinorin A and ketamine on attention in rats. Rats | 2010 | Experimental study | |
| The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Rhesus monkeys | 2004 | Experimental study | n = 3 |
| Antinociceptive and hypothermic effects of Salvinorin A are abolished in a novel strain of kappa-opioid receptor-1 knockout mice. Wild-type mice and kappa-opioid receptor knockout mice | 2006 | Experimental study |
Citations in the library
Cited by 56
- Looking for the Self: Phenomenology, Neurophysiology and Philosophical Significance of Drug-induced Ego Dissolution Frontiers in Human Neuroscience May 23, 2017
- Clinical applications of hallucinogens: A review. Experimental and Clinical Psychopharmacology August 1, 2016
- Models of psychedelic drug action: modulation of cortical-subcortical circuits Brain October 22, 2021
- Potential anxiolytic‐ and antidepressant‐like effects of salvinorin A, the main active ingredient of Salvia divinorum, in rodents British Journal of Pharmacology May 5, 2009
- Dose-related effects of salvinorin A in humans: dissociative, hallucinogenic, and memory effects. Psychopharmacology March 1, 2013
and 51 more in the library
Cites 19
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- Salvinorin A, an active component of the hallucinogenic sage salvia divinorum is a highly efficacious kappa-opioid receptor agonist: structural and functional considerations. Journal of Pharmacology and Experimental Therapeutics March 1, 2004
- Effects of the plant-derived hallucinogen salvinorin A on basal dopamine levels in the caudate putamen and in a conditioned place aversion assay in mice: agonist actions at kappa opioid receptors. Psychopharmacology May 1, 2005
- Ethnopharmacology of ska María Pastora (Salvia divinorum, Epling and Játiva-M.). Journal of Ethnopharmacology May 1, 1983
- Pattern of use and subjective effects of Salvia divinorum among recreational users. Drug and Alcohol Dependence November 8, 2006
and 14 more in the library