Studies in the rat on the haemodynamic overshoot response to withdrawal of guanfacine or clonidine treatment.

1. Normal rats were injected intramuscularly twice daily for either 3 days or 3 weeks with guanfacine (0.1 or 1.0 mg/kg), clonidine (0.01 or 0.1 mg/kg) or 0.9% saline. All were anaesthetized at various times before or after the last injection, and their arterial pressures and heart rates were monitored via a carotid artery catheter. 2. Overshoots in systolic and diastolic pressure and heart rate, reaching peak values as soon as 16 h after the last injection, occurred in all rats withdrawn from guanfacine or clonidine treatment, but in no control rats. 3. Post-withdrawal blood pressures and heart rates of rats which had received the low dose of guanfacine or clonidine were as great as those of rats which had received the ten-fold greater dosage. Moreover, withdrawal responses were as great in rats which had been treated for only 3 days as in those treated for 3 weeks. 4. The dosages and duration of treatments used in these experiments thus did not influence the magnitude of the haemodynamic overshoots provoked by withdrawal of guanfacine or clonidine. However, all groups of rats from which guanfacine was withheld exhibited significantly greater peak overshoots in systolic and diastolic pressure than did those withdrawn from clonidine treatment.