Narcotics and diabetes. I. The effects of streptozotocin-induced diabetes on the antinociceptive potency of morphine.

The antinociceptive potency of morphine as determined by the tail-flick test was significantly decreased in streptozotocin (STZ)-induced diabetic mice and mice pretreated with hypertonic dextrose or fructose. STZ-induced diabetic rats and spontaneously diabetic mice were also significantly less sensitive to the antinociceptive effects of morphine in the tail-flick test. Hypoglycemic mice were significantly more sensitive to morphine. Insulin-reversal of dextrose- and STZ-induced diabetic hyperglycemia returned sensitivity to morphine-induced antinociception to control values. Pretreatment with hypertonic 3-O-methylglucose (a nonmetabolizable sugar) had no effect on morphine potency. The ability of morphine to inhibit phenylquinone-induced writhing was attenuated in STZ-induced diabetic mice. Mice receiving various pretreatments (STZ-induced diabetes, STZ-induced diabetes plus insulin, dextrose, fasting or fasting plus insulin) were subjected to analyses of their serum glucose levels, serum insulin levels and brain glucose lvels. From these data, it appeared that only hyper- or hypoglycemia correlated (inversely) with changes in the potency of morphine. It is hypothesized that the diabetes-induced hyperglycemia is responsible for selectively affecting the potency of morphine.