Delta9-tetrahydrocannabinol-induced conditioned place preference and intracerebroventricular self-administration in rats.
On the basis of contradictory findings on the rewarding effects of Delta9-tetrahydrocannabinol (Delta9-THC) in laboratory animals, the effect of the compound on conditioned place preference and intracerebroventricular (i.c.v.) self-administration in a free-choice procedure, using a wide range of doses (0.015-6 mg/kg for conditioned place preference test and 0.01-1 microg/2 microl/infusion for i.c.v. self-administration), was studied in Wistar rats. The present results showed that Delta9-THC induced reward in both tests, but only at the lowest tested doses (0.075-0.75 mg/kg i.p. for conditioned place preference test and 0.01-0.02 microg/infusion for i.c.v. self-administration). This effect was fully antagonised by i.p. pretreatment with the cannabinoid CB1 receptor antagonist, SR 141716A [N-piperidino-5-(4-chlorophenyl)1-(2,4-dichlorophenyl)-4 methyl pyrazole 3-carboxamide] (0.25-1 mg/kg), and the opiate receptor antagonist, naloxone (0.5-2 mg/kg), suggesting the involvement of both endocannabinoid and opioid systems. In conclusion, these findings demonstrate, for the first time, that low doses of Delta9-THC can act as an effective reinforcer in Wistar rats providing a reliable animal model of human marijuana abuse.
Braida
Daniela
D
Department of Pharmacology, Chemotherapy and Medical Toxicology, Faculty of Sciences, University of Milan, Via Vanvitelli 32, 20129 Milan, Italy.
Iosuè
Stefania
S
Pegorini
Simona
S
Sala
Mariaelvina
M
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors; D000077285:Rimonabant; D012646:Self Administration / Q000379:methods
D009292:Narcotic Antagonists; D010880:Piperidines; D011619:Psychotropic Drugs; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D009270:Naloxone; D013759:Dronabinol; D000077285:Rimonabant