INHIBITORS OF CA2-DEPENDENT ENDOPEPTIDASES MODULATE MORPHINE-INDUCED EFFECTS IN RATS()

The effects of inhibitors of Ca2+-dependent endopeptidases (antipain a nd leupeptin) on morphine analgesia, reinforcing properties of morphin e and on the development of opiate physical dependence were studied. M ale Wistar rats were used. The analgesic action of morphine in the tai l-immersion test was increased significantly by combined injection of morphine with antipain or leupeptin. Antipain or leupeptin alone had n o analgesic action. The combination of morphine with antipain or leupe ptin led to the reduction of morphine-induced place preference and the development of physical dependence. A single injection of antipain di minished the opiate-withdrawal signs in morphine-dependent rats. These results suggest a possible inhibitory effect of antipain or leupeptin on the Ca2+-dependent endopeptidases of neurons that mediate analgesi a, reinforcing properties of morphine, development of opiate dependenc e and withdrawal.