Psychopharmacology

, Volume 210, Issue 2, pp 275–284

Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents

  • D. Matthew Walentiny
  • Robert E. Vann
  • Jonathan A. Warner
  • Lindsey S. King
  • Herbert H. Seltzman
  • Hernán A. Navarro
  • Charles E. TwineJr.
  • Brian F. Thomas
  • Anne F. Gilliam
  • Brian P. Gilmour
  • F. Ivy Carroll
  • Jenny L. Wiley
Original Investigation

DOI: 10.1007/s00213-010-1827-6

Cite this article as:
Walentiny, D.M., Vann, R.E., Warner, J.A. et al. Psychopharmacology (2010) 210: 275. doi:10.1007/s00213-010-1827-6

Abstract

Rationale

Salvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa-opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects.

Objectives

This study represents a systematic examination of this hypothesis.

Methods

Salvinorin A was isolated from S. divinorum and was evaluated in a battery of in vitro and in vivo procedures designed to detect cannabinoid activity, including CB1 receptor radioligand and [35S]GTPγS binding, calcium flux assay, in vivo cannabinoid screening tests, and drug discrimination.

Results

Salvinorin A did not bind to nor activate CB1 receptors. In vivo salvinorin A produced pronounced hypolocomotion and antinociception (and to a lesser extent, hypothermia). These effects were blocked by the selective KOR antagonist, JDTic, but not by the CB1 receptor antagonist rimonabant. Interestingly, however, rimonabant attenuated KOR activation stimulated by U69,593 in a [35S]GTPγS assay. Salvinorin A did not substitute for Δ9-tetrahydrocannabinol (THC) in mice trained to discriminate THC.

Conclusions

These findings suggest that similarities in the pharmacological effects of salvinorin A and those of cannabinoids are mediated by its activation of KOR rather than by any direct action of salvinorin A on the endocannabinoid system. Further, the results suggest that rimonabant reversal of salvinorin A effects in previous studies may be explained in part by rimonabant attenuation of KOR activation.

Keywords

Cannabinoid JDTic Kappa-opioid agonist Kappa-opioid antagonist Rimonabant Salvia divinorum Salvinorin A 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • D. Matthew Walentiny
    • 1
  • Robert E. Vann
    • 1
  • Jonathan A. Warner
    • 1
  • Lindsey S. King
    • 1
  • Herbert H. Seltzman
    • 2
  • Hernán A. Navarro
    • 3
  • Charles E. TwineJr.
    • 2
  • Brian F. Thomas
    • 2
  • Anne F. Gilliam
    • 3
  • Brian P. Gilmour
    • 3
  • F. Ivy Carroll
    • 2
  • Jenny L. Wiley
    • 3
  1. 1.Department of Pharmacology and ToxicologyVirginia Commonwealth UniversityRichmondUSA
  2. 2.Center for Organic and Medicinal ChemistryResearch Triangle InstituteResearch Triangle ParkUSA
  3. 3.Center for Pharmacology and ToxicologyResearch Triangle InstituteResearch Triangle ParkUSA

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