The hallucinogen derived from Salvia divinorum, salvinorin A, has κ-opioid agonist discriminative stimulus effects in rats

Abstract

Data from clinical and preclinical studies converge implicating the plant-derived hallucinogen salvinorin A as an important pharmacologic tool; this psychoactive compound may expand scientific understandings on mammalian κ-opioid receptor systems. Human salvinorin A effects, consistent with κ-opioid receptor agonism, include antinociception, sedation, dysphoria and distorted perceptions. The experiments reported here measured salvinorin A (1–3 mg/kg, i.p.) discriminative stimulus properties in male Sprague–Dawley rats conditioned to recognize the discriminative stimulus cue generated by the well characterized κ-opioid agonist U-69593 (0.56 mg/kg, i.p.). At three distinct active doses, salvinorin A fully substituted for U-69593 without altering response rates. The lever choice pattern in U-69593 trained animals reverted to vehicle lever responding when a kappa selective antagonist compound, nor-BNI (4.5 nM, i.c.v.) was administered 1 h prior to salvinorin A, yet nor-BNI alone failed to impact the rate or pattern of subject responses. These findings confirm and extend results published after similar drug discrimination tests were performed in rhesus monkeys. The discussion section of this article highlights public concern over salvinorin A misuse and emphasizes several potential pharmacotherapeutic applications for salvinorin A or analogue compounds.