Cannabinoid CB(1) antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats.
Rats with a previous history of heroin self-administration were studied to assess interactions occurring between cannabinoids and opioids in an animal model of reinstatement of heroin-seeking behaviour. Rats were trained to self-administer heroin and after a long-term extinction were primed with one of the following non-contingent non-reinforced drug administrations: saline (or vehicle), heroin, synthetic cannabinoid CB(1) receptor agonists (WIN 55,212-2 or CP 55,940), opioid antagonist (naloxone) or CB(1) antagonist (SR 141716A), alone or in combination. After primings, lever-pressing activity was recorded and compared to those observed during previous phases of training and extinction. Results of this study showed that (i) priming injections of heroin (0.1 mg/kg) as well as CB(1) agonists WIN 55,212-2 (0.15 or 0.30 mg/kg) and CP 55,940 (0.05 or 0.1 mg/kg) completely restore heroin-seeking behaviour; (ii) primings of naloxone (1 mg/kg) and SR 141716A (0.3 mg/kg) had no effect when administered alone; (iii) heroin-induced reinstatement was fully prevented by pre-treatment with either naloxone or SR 141716A; (iv) pre-treatment with SR 141716A significantly reduced WIN 55,212-2 and CP 55,940 priming effects. These results suggest that cannabinoid CB(1) receptors play an important role in the mechanisms underlying relapse to heroin-seeking and depict CB(1) antagonists as possible therapeutic agents for use in the prevention of relapse to heroin abuse.
Fattore
Liana
L
Department of Neuroscience and Centre of Excellence on Neurobiology of Dependence, University of Cagliari, Cittadella Universitaria, S.S. 554, 09042 Monserrato, Italy. wfratta@unica.it
Spano
Sabrina
S
Cossu
Gregorio
G
Deiana
Serena
S
Fadda
Paola
P
Fratta
Walter
W
D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control*; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D005108:Extinction, Psychological / Q000187:drug effects*; D003932:Heroin / Q000008:administration & dosage; D006556:Heroin Dependence / Q000517:prevention & control*; D008297:Male; D009025:Morpholines / Q000008:administration & dosage / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009281:Naphthalenes / Q000008:administration & dosage / Q000494:pharmacology; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors*; D000077285:Rimonabant; D012646:Self Administration
D048588:Benzoxazines; D003511:Cyclohexanols; D009025:Morpholines; D009281:Naphthalenes; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D009270:Naloxone; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003932:Heroin; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol; D000077285:Rimonabant