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 via PubMed
Summary
AI-generated from the abstractSalvinorin A, the active compound in Salvia divinorum, increased compulsive gnawing in male C57BL/6 mice when given with apomorphine, indicating dopaminergic activity. This effect was blocked by the dopamine antagonist haloperidol but not by the κ-opioid receptor antagonist NorBNI, suggesting salvinorin A is not a selective κ-opioid receptor agonist. A new digitized method for quantifying gnawing behavior provided more precise measurement of dopaminergic activity.
Study at a glance
| 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 |
| Key finding | 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.