Neuroleptic drugs activate tyrosine hydroxylase of retinal amacrine cells

Tyrosine hydroxylase of retinal dopamine-containing amacrine cells exists in two states, a basal state in the dark and an activated state in the light. Treatment with haloperidol, chlorpromazine, clozapine or domperidone results in activation of tyrosine hydroxylase in the dark. With haloperidol, the magnitude of the activation was dose-related. After a single dose of haloperidol (3 mg/kg i.p.) enzyme activation persisted for at least 3 hr. By kinetic analysis, activation was characterized as a decrease in the Km for the pteridine cofactor. Activation by light induces similar kinetic changes. Apparently, the dopaminergic system of retina responds to neuroleptic drug treatment similar to that nigrostriatal dopaminergic system.