title: Learning and memory impairment induced by salvinorin A, the principal ingredient of Salvia divinorum, in wistar rats.
abstract: The effects of salvinorin A (Salvia divinorum principal ingredient), a potent κ-opioid natural hallucinogen, on learning and memory were investigated. Wistar rats were tested in the 8-arm radial maze, for object recognition and passive avoidance tasks for spatial, episodic, and aversive memory. Attention was assessed using a latent inhibition task. Salvinorin A (80-640 μg/kg subcutaneous [sc]) did not affect short-term memory, but it impaired spatial long-term memory. Episodic and aversive memories were impaired by salvinorin A (160-640 μg/kg). Memory impairment was blocked by the selective κ-opioid receptor antagonist, nor-binaltorphimine ([nor-B]; 0.5-1 mg/kg, intraperitoneal [ip]). Salvinorin A (160 μg/kg) disrupted latent inhibition, after LiCl treatment, such as reduced sucrose intake, suggesting an attention would result in an impairment of cognitive behavior. These findings demonstrate for the first time that salvinorin A has deleterious effects on learning and memory, through a κ-opioid receptor mechanism.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, Universitá degli Studi di Milano, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Braida
authors.forename: Andrea
authors.initials: A
authors.lastname: Donzelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Martucci
authors.forename: Valeria
authors.initials: V
authors.lastname: Capurro
authors.forename: Mariaelvina
authors.initials: M
authors.lastname: Sala
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects; D045785:Diterpenes, Clerodane / Q000633:toxicity*; D006213:Hallucinogens / Q000633:toxicity*; D007266:Inhibition, Psychological; D007858:Learning / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D057567:Memory, Long-Term / Q000187:drug effects*; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D021641:Recognition, Psychology; D027544:Salvia
chemical_list: D045785:Diterpenes, Clerodane; D006213:Hallucinogens; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; C090499:salvinorin A