Cannabinoid CB(1) antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats |
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Authors: | Fattore Liana Spano Sabrina Cossu Gregorio Deiana Serena Fadda Paola Fratta Walter |
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Affiliation: | aDepartment of Neuroscience and Centre of Excellence on Neurobiology of Dependence, University of Cagliari, Cittadella Universitaria, S.S. 554, 09042 Monserrato, Italy bInstitute of Neuroscience, National Research Council CNR, Section of Cagliari, Cagliari, Italy |
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Abstract: | 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 CB1 receptor agonists (WIN 55,212-2 or CP 55,940), opioid antagonist (naloxone) or CB1 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 CB1 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 CB1 receptors play an important role in the mechanisms underlying relapse to heroin-seeking and depict CB1 antagonists as possible therapeutic agents for use in the prevention of relapse to heroin abuse. |
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Keywords: | SR 141716A Cannabinoid Opioid Relapse Reinstatement of heroin-seeking Self administration |
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