Salvinorin A fails to substitute for the discriminative stimulus effects of LSD or ketamine in Sprague–Dawley rats

Abstract

Salvia divinorum is a small perennial shrub that has gained recent popularity among the drug-using subculture as a legal alternative to hallucinogens. Salvinorin A, the main active compound found in the S. divinorum plant, is an atypical hallucinogen with pharmacological selectivity at kappa opioid (KOP) receptor sites and is a unique non-nitrogenous neoclerodane diterpene which is structurally distinct from other opioid compounds. The novel structure of salvinorin A and its specific binding affinity to KOP receptors provide a unique opportunity to investigate neurochemical mechanisms of hallucination and hallucinogenic compounds. The current investigation assessed the substitution of salvinorin A in 16 male Sprague–Dawley rats trained to discriminate either the prototypical serotonergic hallucinogen, LSD (0.08 mg/kg, S.C., n = 8) or the dissociative anesthetic and glutamatergic hallucinogen, ketamine (8.0 mg/kg, I.P., n = 8) from vehicle under a FR 20 schedule of food-reinforced responding. Results indicated that neither LSD nor ketamine discrimination generalized to salvinorin A. These findings are consistent with the growing body of evidence that salvinorin A is pharmacologically distinct from other traditional hallucinogenic compounds.