期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1980
卷号：77
期号：7
页码：4305-4309
DOI：10.1073/pnas.77.7.4305
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Partial, unilateral nigrostriatal lesions of varying severity were produced in rats by injecting graded doses of 6-hydroxydopamine into the substantia nigra. Formation of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid in each surviving nigrostriatal neuron (estimated by the ratios of dihydroxyphenylacetic acid to dopamine and homovanillic acid to dopamine in the striatum) increased significantly when dopamine concentrations in striata containing lesions had been reduced to 25% or less of control values, but remained unchanged in rats with less severe lesions. These findings suggest that, in rats with severe damage of nigrostriatal dopaminergic neurons, surviving neurons increase their firing rates and accelerate dopamine synthesis and release. In rats that had lesions and enhanced striatal dopamine release, but not in rats with lesser lesions (i.e., which reduced ipsilateral dopamine concentrations by less than 75%), administration of tyrosine (250 mg/kg) caused further significant increases in formation of dihydroxyphenylacetic acid and homovanillic acid. These findings provide further evidence that tyrosine availability can enhance dopamine synthesis in and release from nigrostriatal neurons if the firing rates of these neurons are accelerated.
