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Mice withdrawn for 7 days from a 35-day treatment period with haloperidol (3 mg/kg/day) displayed significantly greater spontaneous locomotor activity (hyperkinesia) than animals withdrawn from the vehicle.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suggest that noradrenergic systems are of importance for the manifestation of the hyperkinetic syndrome seen in mice withdrawn from long-term haloperidol treatment.
D000818:Animals; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D006948:Hyperkinesis / Q000209:etiology* / Q000503:physiopathology; D051379:Mice; D009638:Norepinephrine / Q000502:physiology*; D010643:Phenoxybenzamine / Q000494:pharmacology
D010643:Phenoxybenzamine; D005406:Bis(4-Methyl-1-Homopiperazinylthiocarbonyl)disulfide; D006220:Haloperidol; D004298:Dopamine; D009638:Norepinephrine