Cannabinoid CB 1 antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats

Cannabinoid CB 1 antagonist SR 141716A attenuates reinstatement of heroin self-administration in... 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 CB 1 receptor agonists (WIN 55,212-2 or CP 55,940), opioid antagonist (naloxone) or CB 1 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 CB 1 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 CB 1 receptors play an important role in the mechanisms underlying relapse to heroin-seeking and depict CB 1 antagonists as possible therapeutic agents for use in the prevention of relapse to heroin abuse. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

Cannabinoid CB 1 antagonist SR 141716A attenuates reinstatement of heroin self-administration in heroin-abstinent rats

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Publisher
Elsevier
Copyright
Copyright © 2005 Elsevier Ltd
ISSN
0028-3908
eISSN
1873-7064
D.O.I.
10.1016/j.neuropharm.2005.01.022
Publisher site
See Article on Publisher Site

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 CB 1 receptor agonists (WIN 55,212-2 or CP 55,940), opioid antagonist (naloxone) or CB 1 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 CB 1 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 CB 1 receptors play an important role in the mechanisms underlying relapse to heroin-seeking and depict CB 1 antagonists as possible therapeutic agents for use in the prevention of relapse to heroin abuse.

Journal

NeuropharmacologyElsevier

Published: Jun 1, 2005

References

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