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Psychopharmacology (Berl). 2010 Jun;210(2):253-62. doi: 10.1007/s00213-009-1771-5. Epub 2010 Jan 19.

The discriminative effects of the kappa-opioid hallucinogen salvinorin A in nonhuman primates: dissociation from classic hallucinogen effects.

Author information

  • 1Laboratory on the Biology of Addictive Diseases, The Rockefeller University, Box 171, New York, NY 10065, USA. butelme@rockefeller.edu

Abstract

RATIONALE:

The widely available hallucinogen salvinorin A is a unique example of a plant-derived compound selective for kappa-opioid receptors and may produce effects distinct from those of other compounds with classic hallucinogenic or dissociative properties which are also abused in humans.

OBJECTIVES:

The objective of this study is to characterize the salvinorin A discriminative cue in nonhuman primates with high kappa-receptor genetic homology to humans.

METHODS:

Adult rhesus monkeys (n = 3) were trained to discriminate salvinorin A (0.015 mg/kg, s.c.) from vehicle, in a food-reinforced operant discrimination assay. Parallel studies, using unconditioned behavioral endpoints (facial relaxation and ptosis) also evaluated the kappa-opioid receptor mediation of salvinorin A in vivo function.

RESULTS:

Monkeys trained to discriminate salvinorin A generalized structurally diverse, centrally penetrating kappa-agonists (bremazocine, U69,593, and U50,488). By contrast, mu- and delta-opioid agonists (fentanyl and SNC80, respectively) were not generalized, nor were the serotonergic 5HT2 hallucinogen psilocybin or the dissociative N-methyl-D-aspartic acid antagonist, ketamine. The discriminative effects of salvinorin A were blocked by the opioid antagonist quadazocine (0.32 mg/kg), but not by the 5HT2 antagonist ketanserin (0.1 mg/kg). Consistent with these findings, salvinorin and kappa-agonists (e.g., U69,593) produce effects in the unconditioned endpoints (e.g., ptosis), whereas psilocybin was inactive.

CONCLUSIONS:

These findings support the conclusion that the interoceptive/discriminative cue produced by salvinorin A is mediated by agonism at kappa-receptors and is mechanistically distinct from that produced by a classic serotonergic hallucinogen.

PMID:
20084367
[PubMed - indexed for MEDLINE]
PMCID:
PMC2866021
Free PMC Article

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