[Effects of anticholinergics and clozapine on the activation of the striatal dopaminergic system in the rat by haloperidol. Pharmacological findings (author's transl)]

Abstract

Tardive dyskinesias, often seen in patients treated with classical neuroleptics, have been attributed to the development of receptor hypersensitivity following prolonged blockade of dopamine (DA)-receptors. In rats with unilateral striatal lesions, development of DA-receptor hypersensitivity following a 6-day treatment with haloperidol can be demonstrated by means of the increased turning response to apomorphine. Addition of atropine to the haloperidol treatment schedule resulted in a further increase in receptor sensitivity, but with a delay of 24 h in its appearance. This finding provides pharmacological support for the observation that tardive dyskinesias are more frequent and more severe in patients treated with a combination of a classical neuroleptic and an anticholinergic agent. Clozapine, despite its anticholinergic property, did not enhance the haloperidol-induced hypersensitivity.