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Time Course of Adaptations in Dopamine Biosynthesis, Metabolism, and Release Following Nigrostriatal Lesions: Implications for Behavioral Recovery from Brain Injury
Author(s) -
Altar C. Anthony,
Marien Marc R.,
Marshall John F.
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb04106.x
Subject(s) - dopamine , homovanillic acid , dopaminergic , endocrinology , striatum , medicine , 3,4 dihydroxyphenylacetic acid , nigrostriatal pathway , chemistry , biology , substantia nigra , serotonin , receptor
Alterations in neostriatal dopamine metabolism, release, and biosynthesis were determined 3, 5, or 18 days following partial, unilateral destruction of the rat nigrostriatal dopamine projection. Concentrations of dopamine and each of its metabolites, 3,4‐dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 3‐methoxytyra‐mine (3‐MT) were markedly decreased in the lesioned stri‐ata at 3, 5, or 18 days postoperation. The decline in striatal high‐affinity [ 3 H]dopamine uptake closely matched the depletion of dopamine at 3 and 18 days postoperation. However, neither DOPAC, HVA, nor 3‐MT concentrations were decreased to as great an extent as dopamine at any time following lesions that depleted the dopamine innervation of the striatum by >80%. In these more severely lesioned animals, dopamine metabolism, estimated from the ratio of DOPAC or HVA to dopamine, was increased two‐ to fourfold in the injured hemisphere compared with the intact hemisphere. Dopamine release, estimated by the ratio of 3‐MT to dopamine, was more increased, by five‐ to sixfold. Importantly, the HVA/dopamine, DOPAC/dopamine, and 3‐MT/dopamine ratios did not differ between 3 and 18 days postlesioning. The rate of in vivo dopamine biosynthesis, as estimated by striatal DOPA accumulation following 3,4‐dihydroxyphenylalanine (DOPA) decarboxylase inhibition with NSD 1015, was increased by 2.6‐ to 2.7‐fold in the surviving dopamine terminals but again equally at 3 and 18 days postoperation. Thus, maximal increases in dopamine metabolism, release, and biosynthesis occur rapidly within neostriatal terminals that survive a lesion. This mobilization of dopaminergic function could contribute to the recovery from the behavioral deficits of partial denervation by increasing the availability of dopamine to neostriatal dopamine receptors. However, these presynaptic compensations are not sufficient to account for the protracted (at least 3‐week) time course of sensorimotor recovery that has been observed following partial nigrostriatal lesion.