Cardiovascular changes during morphine withdrawal in the rat: effects of clonidine

Arterial blood pressure and heart rate were measured in unrestrained rats as an index of the autonomic component of the morphine withdrawal syndrome. Physical dependence was produced by a constant infusion of morphine at increasing doses over 7 days. Signs of physical dependence observed during abrupt withdrawal included classical behavioral symptoms such as withdrawal body shakes (WBS) and increased autonomic responsiveness which was indicated by a sustained increase in mean arterial pressure (MAP) up to 23 mmHg. Injection of naloxone in morphine dependent rats also evoked a dose-related increase in MAP to about 40 mmHg. The antiwithdrawal effects of clonidine were tested in this model by pretreating dependent rats with this agent (6-60 micrograms/kg). Clonidine inhibited the pressor response produced by naloxone by 23-60%. These findings indicate that the increase in MAP during opiate withdrawal provides an objective and quantitative index of the intensity of the narcotic withdrawal syndrome in dependent rats.