Role of noradrenergic functions in the modification of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes.

The role of noradrenergic functions in the modulation of naloxone-precipitated withdrawal jumping in morphine-dependent mice by diabetes were examined. Both diabetic and non-diabetic mice were chronically treated with morphine (8 - 45 mg/kg, s.c.) for 5 days. During this treatment, neither diabetic nor non-diabetic mice showed any signs of toxicity. After morphine treatment, withdrawal was precipitated by injection of naloxone (0.3 mg/kg, s.c.). The number of naloxone-precipitated withdrawal jumps within 5 min after injection of naloxone was significantly less in morphine-dependent diabetic mice than in morphine-dependent non-diabetic mice. However, there was no significant difference in the number of naloxone-precipitated withdrawal jumps from 5 to 15 min after injection of naloxone between diabetic and non-diabetic mice. The turnover rate of noradrenaline in the frontal cortex in morphine-dependent non-diabetic mice, but not in morphine-dependent diabetic mice, was significantly increased 5 min after administration of naloxone. These results suggest that the functional changes in central noradrenergic systems may be involved in the reduction of naloxone-precipitated jumping in morphine-dependent diabetic mice.