CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoid-seeking behaviour in the rat

1 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. 2 In rats previously trained to intravenously self-administer the synthetic cannabinoid receptor (CB1) agonist WIN 55,212-2 (12.5 ?g kg inf ) 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 ) as well as heroin (0.5 mg kg ), but not cocaine (10 mg kg ), effectively reinstate cannabinoid-seeking behaviour following 3 weeks of extinction. 3 The selective CB1 receptor antagonist SR 141716A (0.3 mg kg 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. 4 The nonselective opioid antagonist naloxone (1 mg kg i.p.) has no effect on operant behaviour per se, but significantly blocks cannabinoid- and heroin-induced reinstatement of cannabinoid-seeking behaviour. 5 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.