title: Involvement of kappa-opioid and endocannabinoid system on Salvinorin A-induced reward.
abstract: BACKGROUND
  The recreational drug, Salvinorin A, derived from the plant of Salvia divinorum, is a potent and selective kappa-opioid receptor agonist. The abuse of selective k-agonists is a novel phenomenon, the mechanism of which is not fully understood.
  
  
  METHODS
  We investigated salvinorin A given SC on the conditioned place preference (.05-160 microg/kg) and intracerebroventricular (ICV) self-administration (.01-1 microg/infusion) paradigms, in Wistar rats.
  
  
  RESULTS
  The present results demonstrate the rewarding effects of Salvinorin A in a range of doses between .1 and 40 microg/kg SC for conditioned place preference test and .1-.5 microg/infusion for ICV self-administration. Highest doses (160 microg/kg for conditioned place preference test and 1 microg/infusion for ICV self-administration) were aversive. The rewarding effect was antagonized by intraperitoneal (IP) pretreatment with the cannabinoid CB(1) receptor antagonist, rimonabant [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichloro phenyl)-4 methyl pyrazole 3-carboxamide] (1 mg/kg), and the kappa-opioid receptor antagonist, nor-binaltorphimine (nor-BNI) (10 mg/kg). In the shell of nucleus accumbens, dopamine extracellular levels were increased after administration of salvinorin A (40 microg/kg SC), reaching a maximum value of about 150%.
  
  
  CONCLUSIONS
  These data provide the demonstration of the rewarding effects of Salvinorin A through an interaction between kappa-opioid and (endo)cannabinoid system in rats.
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Braida
authors.forename: Valeria
authors.initials: V
authors.lastname: Limonta
authors.forename: Valeria
authors.initials: V
authors.lastname: Capurro
authors.forename: Paola
authors.initials: P
authors.lastname: Fadda
authors.forename: Tiziana
authors.initials: T
authors.lastname: Rubino
authors.forename: Paola
authors.initials: P
authors.lastname: Mascia
authors.forename: Alessia
authors.initials: A
authors.lastname: Zani
authors.forename: Enzo
authors.initials: E
authors.lastname: Gori
authors.forename: Walter
authors.initials: W
authors.lastname: Fratta
authors.forename: Daniela
authors.initials: D
authors.lastname: Parolaro
authors.forename: Mariaelvina
authors.initials: M
authors.lastname: Sala
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000037:antagonists & inhibitors / Q000502:physiology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004224:Diterpenes / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004347:Drug Interactions; D063388:Endocannabinoids; D008297:Male; D017551:Microdialysis / Q000379:methods; D009043:Motor Activity / Q000187:drug effects; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D012201:Reward; D000077285:Rimonabant; D012646:Self Administration
chemical_list: D000975:Antioxidants; D063385:Cannabinoid Receptor Modulators; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D063388:Endocannabinoids; D009292:Narcotic Antagonists; D010880:Piperidines; D011720:Pyrazoles; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D000077285:Rimonabant; C090499:salvinorin A; D004298:Dopamine