Withdrawal syndrome after continuous infusion of clonidine in the normotensive rat

The effects on heart rate and arterial pressure of continuous subcutaneous infusion of clonidine (500 microgram kg-1 day-1) via an ALZET miniosmopump and sudden termination of this treatment were studied in conscious normotensive rats. No consistent decreases of heart rate and blood pressure were observed during the clonidine infusion. Within a few hours following removal of the minipumps, a pronounced and long-lasting tachycardia developed. Mean arterial pressure did not exceed control level consistently, but transient blood pressure 'upswings' were observed. The withdrawal phenomena were accompanied by a small, significant rise in plasma noradrenaline content. During the clonidine-infusion period piloerection and sedation were prominent. The present study indicates, that the occurrence of the withdrawal phenomena following cessation of clonidine treatment is not dependent upon a decrease of blood pressure and heart rate preceding clonidine withdrawal. Furthermore, the model presented may be suitable for the study of withdrawal phenomena of other anti-hypertensive drugs.