The hallucinogen derived from Salvia divinorum, salvinorin A, has kappa-opioid agonist discriminative stimulus effects in rats.
Neuropharmacology – September 01, 2007
Source: PubMed
Summary
A plant-derived compound known for its hallucinogenic properties offers surprising insights into brain chemistry. Scientists investigated how this psychoactive compound interacts with specific brain receptors. Rats were trained to recognize the effects of a known kappa-opioid activator. Remarkably, the plant compound produced identical effects, indicating it powerfully stimulates these same receptors. This was further confirmed when a blocking agent prevented its actions, directly linking its effects to the kappa-opioid system. This discovery solidifies the compound's role as a valuable tool for understanding pain relief, mood regulation, and perception, opening doors for potential new therapeutic developments.
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 kappa-opioid receptor systems. Human salvinorin A effects, consistent with kappa-opioid receptor agonism, include antinociception, sedation, dysphoria and distorted perceptions. The experiments reported here measured salvinorin A (1-3mg/kg, i.p.) discriminative stimulus properties in male Sprague-Dawley rats conditioned to recognize the discriminative stimulus cue generated by the well characterized kappa-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 1h 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.