Markers of dopamine depletion and compensatory response in striatum and cerebrospinal fluid |
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Authors: | D A Loeffler P A LeWitt A J DeMaggio P L Juneau P E Milbury and W R Matson |
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Institution: | (1) Present address: Clinical Neuroscience Laboratory, Research Building, Room 209, Sinai Hospital, 6767 West Outer Drive, 48235 Detroit, Michigan, U.S.A.;(2) Departments of Neurology and Psychiatry, Wayne State University School of Medicine, Detroit, Michigan, U.S.A.;(3) Cellular and Clinical Neuroscience Program, Wayne State University School of Medicine, Detroit, Michigan, U.S.A.;(4) Preclinical Biometrics, Warner Lambert Company, Ann Arbor, Michigan, U.S.A.;(5) ESA, Incorporated, Chelmsford, Massachusetts, U.S.A. |
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Abstract: | Summary Though depletion of CSF homovanillic acid (HVA) concentration has often been regarded as a direct indicator of dopamine (DA) deficiency in Parkinson's Disease (PD), CSF HVA is normal in mildly affected patients. To explore why, we measured DA and its metabolites in striatum and CSF in rabbits receiving reserpine for 5 days. Reserpine, which depletes striatal DA by disrupting vesicular storage of the neurotransmitter, results in a compensatory increase of DA turnover. In response to a 96% depletion of striatal DA, its catabolic intermediates 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) decreased 64% and 92% in striatum, although the endproduct, HVA, was unchanged. In contrast, CSF concentrations of HVA and DOPAC increased significantly, though 3-MT and levodopa (LD) were unaltered. A 5-fold rise in striatal LD concentration after reserpine-induced DA depletion provided evidence for enhanced DA synthesis. As in PD, the compensatory increase of DA synthesis after reserpine administration confounds the ability of CSF HVA to reflect DA depletion. |
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Keywords: | Parkinson's disease cerebrospinal fluid dopamine reserpine homovanillic acid |
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