Reduction of opioid dependence by the CB1 antagonist SR141716A in mice: evaluation of the interest in pharmacotherapy of opioid addiction

1 Several compounds, mainly opioid agonists such as methadone, are currentl y used for long term medication of heroin addicts. Nevertheless, these main tenance treatments have the disadvantage to induce a dependence to another opiate. As interactions between opioid and cannabinoid systems have been de monstrated, the ability of the CB1 antagonist, SR141716A to reduce morphine -induced addiction was investigated. 2 The effects of SR141716A on the rewarding responses of morphine were eval uated in the place conditioning paradigm. No significant conditioned prefer ence or aversion were observed after repeated treatment with the CB1 antago nist alone. However, SR141716A was able to antagonize the acquisition of mo rphine-induced conditioned place preference. 3 SR141716A was co-administered with morphine for 5 days, and the withdrawa l syndrome was precipitated by naloxone administration. A reduction in the incidence of two main signs of abstinence: wet dog shakes and jumping was o bserved while the other were not significantly modified. In contrast, an ac ute injection of the CB1 antagonist just before naloxone administration was unable to modify the incidence of the behavioural manifestations of the wi thdrawal, suggesting that only chronic blockade of CB1 receptors is able to reduce morphine-induced physical dependence. 4 Several biochemical mechanisms could explain the reduction of opioid depe ndence 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 possib le use in opioid addiction.