Time Course of Adaptations in Dopamine Biosynthesis, Metabolism, and Release Following Nigrostriatal Lesions: Implications for Behavioral Recovery from Brain Injury

Time Course of Adaptations in Dopamine Biosynthesis, Metabolism, and Release Following... Abstract: 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 (3H)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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Time Course of Adaptations in Dopamine Biosynthesis, Metabolism, and Release Following Nigrostriatal Lesions: Implications for Behavioral Recovery from Brain Injury

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Publisher
Wiley
Copyright
Copyright © 1987 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1987.tb04106.x
Publisher site
See Article on Publisher Site

Abstract

Abstract: 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 (3H)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.

Journal

Journal of NeurochemistryWiley

Published: Feb 1, 1987

References

  • On the significance of endogenous 3‐methoxytyramine for the effects of centrally acting drugs on dopamine release in the rat brain
    Westerink, Westerink; Spaan, Spaan

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