Destruction of post-synaptic dopamine receptors prevents neuroleptic-induced activation of striatal tyrosine hydroxylase but not dopamine synthesis stimulation.

Destruction of post-synaptic dopamine (DA)-receptors by intrastriatal kainic acid prevents the haloperidol-induced activation of striatal tyrosine-hydroxylase but not the stimulation of DA-synthesis estimated in vivo on the accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of aromatic aminoacid decarboxylase. The results indicate the existence of two DA-receptor-mediated mechanisms regulating DA-synthesis in vivo: one depending on the presence of post-synaptic DA-receptors and capable of producing a stable activation of tyrosine-hydroxylase whereas the other is not associated to a persistent conformational change of tyrosine-hydroxylase and is possibly mediated by pre-synaptic DA-receptors. The results also indicate that the activation of striatal tyrosine-hydroxylase by neuroleptics is unrelated to blockade of pre-synaptic DA-receptors.