title: CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoid-seeking behaviour in the rat.
abstract: We recently provided evidence for a functional link between cannabinoid and opioid endogenous systems in relapse to heroin-seeking behaviour in rats. In the present study, we aimed at investigating whether the previously observed cross-talk between cannabinoids and opioids could be extended to mechanisms underlying relapse to cannabinoid-seeking behaviour after a prolonged period of abstinence. In rats previously trained to intravenously self-administer the synthetic cannabinoid receptor (CB1) agonist WIN 55,212-2 (12.5 microg kg(-1) inf(-1)) under a fixed ratio (FR1) schedule of reinforcement, noncontingent nonreinforced intraperitoneal (i.p.) priming injections of the previously self-administered CB1 agonist (0.25 and 0.5 mg kg(-1)) as well as heroin (0.5 mg kg(-1)), but not cocaine (10 mg kg(-1)), effectively reinstate cannabinoid-seeking behaviour following 3 weeks of extinction. The selective CB1 receptor antagonist SR 141716A (0.3 mg kg(-1) i.p.) does not reinstate responding when given alone, but completely prevents the cannabinoid-seeking behaviour triggered by WIN 55,212-2 or heroin primings. The nonselective opioid antagonist naloxone (1 mg kg(-1) i.p.) has no effect on operant behaviour per se, but significantly blocks cannabinoid- and heroin-induced reinstatement of cannabinoid-seeking behaviour. These results provide the first evidence of drug-induced reinstatement of cannabinoid-seeking behaviour, and further strengthen previous findings on a cross-talk between the endogenous cannabinoid and opioid systems in relapse mechanisms to drug-seeking.
authors.affiliation: Department of Neuroscience and Centre of Excellence Neurobiology of Dependence, Cittadella Universitaria di Monserrato, University of Cagliari, Italy.
authors.forename: M Sabrina
authors.initials: MS
authors.lastname: Spano
authors.forename: Liana
authors.initials: L
authors.lastname: Fattore
authors.forename: Gregorio
authors.initials: G
authors.lastname: Cossu
authors.forename: Serena
authors.initials: S
authors.lastname: Deiana
authors.forename: Paola
authors.initials: P
authors.lastname: Fadda
authors.forename: Walter
authors.initials: W
authors.lastname: Fratta
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D048588:Benzoxazines; D002186:Cannabinoids / Q000008:administration & dosage*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D005108:Extinction, Psychological; D003932:Heroin / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D000077285:Rimonabant; D012646:Self Administration; D013997:Time Factors
chemical_list: D048588:Benzoxazines; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D009292:Narcotic Antagonists; 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; D003042:Cocaine; D000077285:Rimonabant