Studies on clonidine and guanfacine withdrawal after short term treatment in the rat.

Abrupt cessation of chronic, but not acute, clonidine treatment has been shown to produce a withdrawal syndrome in man. Guanfacine, its analogue, causes little or no such effect. Some animal models of clonidine and guanfacine withdrawal have shown significant changes in blood pressure and heart rate after both acute and chronic administration of the drugs. We administered both drugs to rats using a dosage schedule which we had shown to produce hypertension and tachycardia when clonidine, but not guanfacine, was stopped after 3 weeks treatment. After 3 days treatment both drugs were withdrawn. There was no significant alteration of blood pressure in either group. A small (3%) tachycardia in the clonidine treated group was the only significant variation from control. This suggests that in this animal model, as in man, clonidine withdrawal phenomena can be seen only after stopping chronic, not acute treatment. Guanfacine withdrawal phenomena were not observed.