A new digitized method of the compulsive gnawing test revealed dopaminergic activity of salvinorin A in vivo.
Stephen M Phipps, Veronika Butterweck
Planta Medica September 1, 2010 DOI: 10.1055/s-0029-1240954 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male C57BL/6 mice |
| Interventions | Salvinorin A buproprion nomifensine apomorphine U-69593 norbinaltorphimine haloperidol |
| Dose | 20 mg/kg buproprion, 10 mg/kg nomifensine, 10 mg/kg apomorphine, 1.0, 2.5, 5, and 10 mg/kg salvinorin A, 10 and 20 mg/kg NorBNI, 0.06 mg/kg haloperidol |
| Topics | Salvia divinorum |
| Key findings | Salvinorin A shows dopaminergic activity in mice that is not mediated solely by κ-opioid receptors, as its effect was blocked by haloperidol but not by NorBNI. |
Abstract
The compulsive gnawing (CG) test has been used for numerous years as an assay to determine the dopaminergic activity of various compounds. We developed a new method of quantification via a digitization step which allowed a more precise measurement of the gnawing activity. It was the aim of the present study to explore possible dopaminergic effects of salvinorin A (SA), the major active compound of Salvia divinorum, using the new digitized CG test. A group of experiments using male C57BL/6 mice were performed to validate the new method of quantification showing only significant increases of gnawing when the dopamine reuptake inhibitors buproprion (20 mg/kg, p.0.) and nomifensine (10 mg/kg, i.p.) were given concomitantly with apomorphine (10 mg/kg, i.p.). Different concentrations of the SA (1.0, 2.5, 5, and 10 mg/kg, i.p.) were tested with positive dopaminergic activity when administered with apomorphine which differed from the semisynthetic counterpart U-69593. Furthermore, the activity observed with SA was unsuccessfully antagonized by the κ-opioid receptor antagonist norbinaltorphimine (NorBNI; 10 and 20 mg/kg, i.p.), while the dopamine antagonist haloperidol did successfully block (0.06 mg/kg, i.p.) the gnawing activity seen with SA. Our data further strengthen the argument that salvinorin A is not a selective κ-opioid receptor agonist and is the first in vivo study that veers from salvinorin A acting solely like its synthetic counterparts. Furthermore, the digitized CG test system used in this study provides a new computational method to accurately detect behavior associated with dopaminergic neurotransmission.
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 | |
| Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward. Wistar rats | 2008 | 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 |
Citations in the library
Cited by 3
- Neuropharmacology of the naturally occurring kappa-opioid hallucinogen salvinorin A. Pharmacological Reviews June 1, 2011
- From local to global-fifty years of research on Salvia divinorum. Journal of Ethnopharmacology February 3, 2014
- Preparation of neoclerodane diterpenes as probes for the opioid receptor system July 1, 2010
Cites 11
- Salvinorin A: a potent naturally occurring nonnitrogenous kappa opioid selective agonist. Proceedings of the National Academy of Sciences September 3, 2002
- 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
- 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
- The plant-derived hallucinogen, salvinorin A, produces kappa-opioid agonist-like discriminative effects in rhesus monkeys. Psychopharmacology March 1, 2004
- Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil. Synapse August 1, 2009
and 6 more in the library