Histamine H3-receptor activation inhibits dopamine synthesis in rat striatum

Unilateral 6-hydroxydopamine lesion to rat substantia nigra pars compacts resulted in a modest, but significant, decrease in the specific binding of N-alpha-[methyl-H-3]histamine (19+/-5% reduction) to synaptosomal membranes from ipsilateral striata. Dopamine synthesis was assessed in striatal slices by determining [H-3]DOPA accumulation after inhibition of DOPA decarboxylase. [H-3]DOPA synthesis induced by 50 mM K+ (151+/-4% of basal) was prevented by either Ca2+ removal or by Ni2+. Depolarization-stimulated [H-3]DOPA accumulation was reduced by the selective H-3-agonist immepip (100 nM; 68+/-7% inhibition). The effect of immepip was reversed by thioperamide (100 nM), a selective H-3-antagonist. Taken together, our results indicate that histamine modulates striatal dopamine synthesis by acting at H-3-receptors located on dopaminergic nerve terminals. NeuroReport 11:163-166 (C) 2000 Lippincott Williams & Wilkins.