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

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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 μg 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 sè, 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. British Journal of Pharmacology (2004) 143, 343–350. doi:10.1038/sj.bjp.0705932

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