Hyperglycemic suppression of morphine withdrawal signs in the rat.

Male Sprague-Dawley rats maintained under controlled lighting and temperature conditions were used in this experiment. Morphine dependency was induced by giving increasing doses of morphine by intraperitoneal injection (IP group) or by the ingestion of morphine through drinking water (PO group). Animals were injected with 10, 20, 30 and 50 mg/kg morphine sulfate at days 1, 2, 3 and 4, respectively. Another group of animals received increasing concentrations of morphine through drinking water from 0.1, 0.2, 0.3 to 0.4 mg/ml at 48 h intervals. Morphine dependent animals were given naloxone by the intraperitoneal route to precipitate withdrawal. Glucose (3 g/kg or 10 g/kg) was given 10 min prior to the administration of naloxone to the respective groups. Another two groups of animals were made diabetic by the administration of streptozotocin. In one group, animals received increasing concentrations of 10, 20, 30 and 50 mg/kg morphine sulfate by the IP route at days 1, 2, 3 and 4, while the other group was not treated with morphine but was assessed for withdrawal signs to serve as the control. Withdrawal signs were assessed by observing the presence of diarrhea, tremor, piloerection, hunchbacked posture, teeth chattering, salivation, erection, restless activity, territorial exploring, irritability to handling, vocalization and jumping. Results obtained indicate that glucose administration at 10 g/kg abolished most of the withdrawal signs, and we were unable to induce the same degree of morphine dependency in diabetic animals as compared to the non-diabetic groups. It was concluded from this study that hyperglycemia could suppress morphine withdrawal signs.