Involvement of cannabinoid CB1 receptors in drug addiction: effects of rimonabant on behavioral responses induced by cocaine.
A lot of evidence indicate that endocannabinoids and cannabinoid CB(1) receptors are implicated in drug addiction. In the present study, we investigated the effect of the cannabinoid CB(1) receptor antagonist/partial agonist rimonabant on the cocaine-maintained reinforcement and relapse to cocaine seeking as well as on the cocaine challenge-induced hyperactivity in sensitized rats and on discriminative stimulus effects of cocaine in rats. We found that endocannabinoids were not involved in maintenance of cocaine reinforcement and its subjective effects since pharmacological blockade of cannabinoid CB(1) receptors altered neither self-administration nor discriminative stimulus effects of cocaine. On the other hand, withdrawal from repeated access or exposure to cocaine and then a reinstatement of cocaine-seeking behavior or a sensitized locomotor response to a single cocaine challenge, respectively, was potently reduced by pretreatment with rimonabant. The latter observations may show that repeated cocaine treatment and the drug withdrawal produce--apart from behavioral effects--also different neural consequences in the endocannabinoid systems in rats.
Filip
Małgorzata
M
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. filip@if-pan.krakow.pl
Gołda
Anna
A
Zaniewska
Magdalena
M
McCreary
Andrew C
AC
Nowak
Ewa
E
Kolasiewicz
Wacław
W
Przegaliński
Edmund
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000209:etiology*; D004193:Discrimination Learning / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077285:Rimonabant; D012646:Self Administration
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D003042:Cocaine; D000077285:Rimonabant