THE INFLUENCE OF CHRONIC TREATMENT WITH CLONIDINE, YOHIMBINE AND IDAZOXAN ON MORPHINE-WITHDRAWAL

Numerous previous attempts have been made to study the involvement of alpha(2)-adrenoceptors in the expression of morphine withdrawal by stu dying the effects of selective alpha(2)-agonists and antagonists admin istered immediately before precipitation of withdrawal by an opioid an tagonist such as naloxone, In the present investigation, we examined t he effects of chronic treatment with clonidine (alpha(2)-agonist), ida zoxan and yohimbine (alpha(2)-antagonists), concomitantly administered with morphine, on the expression of the withdrawal signs. In contrast to their acute effects, clonidine potentiated, while yohimbine and id azoxan attenuated the withdrawal signs precipitated by naloxone in mor phine-dependent mice. In addition, mice chronically treated only with yohimbine displayed withdrawal signs similar to those reported with mo rphine withdrawal and these signs were not influenced by naloxone admi nistration. Mice chronically treated with clonidine displayed withdraw al signs similar to those reported with morphine withdrawal and these signs were further potentiated by naloxone administration. The results suggest that down-regulation of az-adrenoceptors by morphine is a maj or adaptation contributing to development of dependence on opioids and also point the way to more effective treatment of narcotic dependence . This suggestion was based on the hypothesis that the suppression of noradrenergic system during chronic morphine treatment by alpha(2)-ant agonists might diminish noradrenergic hyperactivity and consequently t he development of dependence and withdrawal signs.