Activation of tyrosine hydroxylase by haloperidol in fetal nigral transplants

Release of dopamine (DA) from the terminals of solid fetal mesencephalic grafts has been shown to be modulated by DA receptor activity. In order to determine whether DA synthesis in the terminals of these grafts is regulated by the host, we examined the activity of tyrosine hydroxylase (TH), the rate limiting enzyme in the synthesis of dopamine, after blockade of DA receptors with haloperidol (HAL). Solid fetal mesencephalic tissue was grafted over the dorsal surface of the striatum, ipsilateral to a 6-hydroxydopamine lesion in the medial forebrain bundle. Systemic administration of HAL caused an activation of TH in the transplant terminals, reflected by an increased affinity of TH for the pteridine cofactor. Our results indicate that a transneuronal feedback mechanism similar to that operating in the intact nigrostriatal system is regulating DA synthesis and utilization in the terminals of the transplant.