A comparison of the inhibitory effects of clonidine and guanfacine on the behavioral and autonomic components of morphine withdrawal in rats.

Intravenous administration of naloxone (0.5 mg/kg) to morphine dependent rats elicited classical autonomic and behavioral symptoms of narcotic abstinence including hypertension, tachycardia, withdrawal body shakes, escape attempts, diarrhea, etc. Pretreatment of dependent rats with either clonidine (3-90 micrograms/kg) or guanfacine (3-900 micrograms/kg) produced a dose-dependent reduction in the hypertensive response to subsequent injection of naloxone. Clonidine was about 12 times more potent than guanfacine in inhibiting this autonomic symptom of withdrawal. Both drugs were less effective at blocking body shakes and escapes, however, when all symptoms were combined in a ranked score, guanfacine was less effective than clonidine at reducing the ranked abstinence intensity score. Since clonidine blocked the autonomic component of withdrawal at doses more consistent with its clinical anti-withdrawal actions, it is possible that 1) measurement of behavioral signs of withdrawal in rats is a less sensitive index than is measurement of autonomic changes associated with withdrawal, or, 2) a reduction in autonomic outflow in general is most relevant to suppressing the apparent intensity of the abstinence syndrome.