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Histamine H3-receptor activation inhibits dopamine synthesis in rat striatum

Molina-Hernández, Anayansi1; Nuñez, Alejandro1; Arias-Montaño, José-Antonio1,2

Neuropharmacology and Neurotoxicology

Unilateral 6-hydroxydopamine lesion to rat substantia nigra pars compacta resulted in a modest, but significant, decrease in the specific binding of N-α-[methyl-3H]histamine (19 ± 5% reduction) to synaptosomal membranes from ipsilateral striata. Dopamine synthesis was assessed in striatal slices by determining [3H]DOPA accumulation after inhibition of DOPA decarboxylase. [3H]DOPA synthesis induced by 50 mM K+ (151 ± 4% of basal) was prevented by either Ca2+ removal or by Ni2+. Depolarization-stimulated [3H]DOPA accumulation was reduced by the selective H3-agonist immepip (100 nM; 68 ± 7% inhibition). The effect of immepip was reversed by thioperamide (100 nM), a selective H3-antagonist. Taken together, our results indicate that histamine modulates striatal dopamine synthesis by acting at H3-receptors located on dopaminergic nerve terminals.

1Departmento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados, Apdo. postal 14-740, 07000 México DF, México

2Corresponding Author: José-Antonio Arias-Montaño

Acknowledgements: Supported by CINVESTAV and CONACYT (grant 28276N). A.M.H. is the recipient of a CONACYT predoctoral scholarship.

Received 1 September 1999; accepted 3 November 1999

© 2000 Lippincott Williams & Wilkins, Inc.