title: 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 (0.08mg/kg, S.C., n=8) or the dissociative anesthetic and glutamatergic hallucinogen, ketamine (8.0mg/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.
authors.affiliation: Department of Psychology, Western Michigan University, Kalamazoo, MI 49008-5439, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Killinger
authors.forename: Mary M
authors.initials: MM
authors.lastname: Peet
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Baker
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D045785:Diterpenes, Clerodane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012055:Reinforcement Schedule
chemical_list: D045785:Diterpenes, Clerodane; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D011619:Psychotropic Drugs; D016194:Receptors, N-Methyl-D-Aspartate; D007649:Ketamine; D008238:Lysergic Acid Diethylamide; C090499:salvinorin A