Reduction of opioid dependence by the CB 1 antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction

Reduction of opioid dependence by the CB 1 antagonist SR141716A in mice: evaluation of the... Several compounds, mainly opioid agonists such as methadone, are currently used for long term medication of heroin addicts. Nevertheless, these maintenance treatments have the disadvantage to induce a dependence to another opiate. As interactions between opioid and cannabinoid systems have been demonstrated, the ability of the CB1 antagonist, SR141716A to reduce morphine‐induced addiction was investigated. The effects of SR141716A on the rewarding responses of morphine were evaluated in the place conditioning paradigm. No significant conditioned preference or aversion were observed after repeated treatment with the CB1 antagonist alone. However, SR141716A was able to antagonize the acquisition of morphine‐induced conditioned place preference. SR141716A was co‐administered with morphine for 5 days, and the withdrawal syndrome was precipitated by naloxone administration. A reduction in the incidence of two main signs of abstinence: wet dog shakes and jumping was observed while the other were not significantly modified. In contrast, an acute injection of the CB1 antagonist just before naloxone administration was unable to modify the incidence of the behavioural manifestations of the withdrawal, suggesting that only chronic blockade of CB1 receptors is able to reduce morphine‐induced physical dependence. Several biochemical mechanisms could explain the reduction of opioid dependence by CB1 antagonists. Whatever the hypotheses, this study supports the reported interaction between the endogenous cannabinoid and opioid systems, and suggests that SR 141716A warrants further investigations for a possible use in opioid addiction. British Journal of Pharmacology (2001) 132, 1809–1816; doi:10.1038/sj.bjp.0703990 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png British Journal of Pharmacology Wiley

Reduction of opioid dependence by the CB 1 antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction

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Publisher
Wiley
Copyright
2001 British Pharmacological Society
ISSN
0007-1188
eISSN
1476-5381
D.O.I.
10.1038/sj.bjp.0703990
Publisher site
See Article on Publisher Site

Abstract

Several compounds, mainly opioid agonists such as methadone, are currently used for long term medication of heroin addicts. Nevertheless, these maintenance treatments have the disadvantage to induce a dependence to another opiate. As interactions between opioid and cannabinoid systems have been demonstrated, the ability of the CB1 antagonist, SR141716A to reduce morphine‐induced addiction was investigated. The effects of SR141716A on the rewarding responses of morphine were evaluated in the place conditioning paradigm. No significant conditioned preference or aversion were observed after repeated treatment with the CB1 antagonist alone. However, SR141716A was able to antagonize the acquisition of morphine‐induced conditioned place preference. SR141716A was co‐administered with morphine for 5 days, and the withdrawal syndrome was precipitated by naloxone administration. A reduction in the incidence of two main signs of abstinence: wet dog shakes and jumping was observed while the other were not significantly modified. In contrast, an acute injection of the CB1 antagonist just before naloxone administration was unable to modify the incidence of the behavioural manifestations of the withdrawal, suggesting that only chronic blockade of CB1 receptors is able to reduce morphine‐induced physical dependence. Several biochemical mechanisms could explain the reduction of opioid dependence by CB1 antagonists. Whatever the hypotheses, this study supports the reported interaction between the endogenous cannabinoid and opioid systems, and suggests that SR 141716A warrants further investigations for a possible use in opioid addiction. British Journal of Pharmacology (2001) 132, 1809–1816; doi:10.1038/sj.bjp.0703990

Journal

British Journal of PharmacologyWiley

Published: Apr 1, 2001

References

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    HARRIS, HARRIS; WATERS, WATERS; MCLENDON, MCLENDON
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    KREEK, KREEK
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