The hyperkinetic syndrome following long-term haloperidol treatment: involvement of dopamine and noradrenaline.

Mice withdrawn for 7 days from a 35-day treatment period with haloperidol (3 mg/kg/day) displayed significantly greater spontaneous locomotor activity (hyperkinesia) than animals withdrawn from the vehicle. The hyperkinesia was antagonized by phenoxybenzamine (an alpha-adrenergic receptor antagonist) and by FLA-63 (a dopamine-beta-hydroxylase inhibitor) but not by haloperidol (a dopamine receptor antagonist). alpha-Methyl tyrosine (a tyrosine hydroxylase inhibitor) was effective in antagonizing the hyperkinesia and this blockade by alpha-methyl tyrosine could be completely reversed by the administration of a low dose of the catecholamine precursor, DOPA. The data suggest that noradrenergic systems are of importance for the manifestation of the hyperkinetic syndrome seen in mice withdrawn from long-term haloperidol treatment.