Cardiovascular changes during morphine administration and spontaneous withdrawal in the rat.

Morphine maintenance doses of 10 mg kg(-1) day(-1), 20 mg kg(-1) day(-1) and 30 mg kg(-1) day(-1) were administered to three groups of rats via miniosmotic pumps for 7 days to induce physical dependence. They were then allowed to undergo spontaneous withdrawal. Radiotelemetric blood pressure measurements showed that morphine increased systolic and diastolic blood pressure on the first day of morphine treatment and produced a dose dependent decrease in heart rate, systolic and diastolic blood pressure thereafter. After the peak depressive effect, development of tolerance to morphine was observed in systolic and diastolic blood pressure, but not in the heart rate. During spontaneous withdrawal, both systolic and diastolic blood pressure increased beyond pre-morphine levels for all doses and there was a rebound increase in heart rate at the 30 mg kg(-1) day(-1) dose. These results suggest that the improved sensitivity of telemetric measures combined with the use of minipumps for morphine treatment provide an animal model of spontaneous opioid withdrawal.