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- Title
CB1 receptor agonist and heroin, but not cocaine, reinstate cannabinoid-seeking behaviour in the rat.
- Authors
Spano, M. Sabrina; Fattore, Liana; Cossu, Gregorio; Deiana, Serena; Fadda, Paola; Fratta, Walter
- 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.
- Subjects
DRUG receptors; OPERANT behavior; CANNABINOIDS; OPIOIDS; HEROIN; RATS; ANIMAL behavior; ANIMAL experimentation; CELL receptors; COCAINE; COMPARATIVE studies; HETEROCYCLIC compounds; HYDROCARBONS; RESEARCH methodology; MEDICAL cooperation; NALOXONE; NARCOTIC antagonists; PIPERIDINE; REINFORCEMENT (Psychology); RESEARCH; SELF medication; TIME; EVALUATION research; PHARMACODYNAMICS; CELL physiology
- Publication
British Journal of Pharmacology, 2004, Vol 143, Issue 3, p343
- ISSN
0007-1188
- Publication type
journal article
- DOI
10.1038/sj.bjp.0705932