Morphine dependence and diabetes. I. The development of morphine dependence in streptozotocin-diabetic rats and spontaneously diabetic C57BL/KsJ mice.

Spontaneously diabetic (db/db) and nondiabetic (db/m+, m+/m+) C57BL/KsJ mice were made dependent by a 9-day exposure to increasing doses of morphine-admixed food. Radioimmunoassay for morphine demonstrated that diabetic mice had significantly greater brain accumulations of morphine than nondiabetic littermates after morphine-admixed food. Despite their greater brain levels of morphine, diabetic mice showed significantly fewer behavioral signs of withdrawal after naloxone, and lost significantly less weight at 60 min after naloxone than their nondiabetic littermates. Streptozotocin-diabetic and nondiabetic rats rendered dependent by a 6-day i.p. infusion of morphine had equal brain levels of morphine, but the diabetic rats showed significantly fewer behavioral signs of withdrawal than nondiabetic rats at 24 and 48 hr after the end of the infusion. These results indicate that spontaneously diabetic mice and streptozotocin-diabetic rats were both significantly less physically dependent upon morphine than their respective nondiabetic controls and support our conclusion that the development of physical dependence upon morphine is reduced in experimental models of diabetes.