Chronic haloperidol and adrenergic receptor sensitivity in the rat

Rats were administered haloperidol (3-4 mg/kg/day) in their drinking water for 42 days, and experiments conducted on the seventh day of withdrawal. Anaesthetized haloperidol treated rats exhibited a similar mean blood pressure (BP) and heart rate (HR) response to control rats when challenged with phenylephrine (IV). When similarly pretreated rats were challenged with one of four possible doses of clonidine (IV), haloperidol treated rats were less sensitive than control rats to clonidine's hypertensive action, but there were no effects of treatment on the hypotensive (BP) effect of clonidine nor on its bradycardic effect. When one of six possible doses of tyramine was administered a similar mean BP response was seen in both treatment groups, but the positive HR response in the haloperidol-treated group was much less than in the vehicle-treated group. Atria isolated from haloperidol treated or control rats revealed a similar chronotropic response to noradrenaline and tyramine challenge. These data indicate that chronic haloperidol does not cause a generalized change in alpha-adrenergic receptor sensitivity. Nevertheless, it is clear that haloperidol has produced changes in the cardiovascular response of rats to these drugs.