MARKERS OF DOPAMINE DEPLETION AND COMPENSATORY RESPONSE IN STRIATUM AND CEREBROSPINAL-FLUID

Though depletion of CSF homovanillic acid (HVA) concentration has ofte n been regarded as a direct indicator of dopamine (DA) deficiency in P arkinson's Disease (PD), CSF HVA is normal in mildly affected patients . To explore why, we measured DA and its metabolites in striatum and C SF in rabbits receiving reserpine for 5 days. Reserpine, which deplete s striatal DA by disrupting vesicular storage of the neurotransmitter, results in a compensatory increase of DA turnover. In response to a 9 6% depletion of striatal DA, its catabolic intermediates 3,4-dihydroxy phenylacetic acid (DOPAC) and 3-methoxytyramine (3-MT) decreased 64% a nd 92% in striatum, although the endproduct, HVA, was unchanged. In co ntrast, CSF concentrations of HVA and DOPAC increased significantly, t hough 3-MT and levodopa (LD) were unaltered. A 5-fold rise in striatal LD concentration after reserpine-induced DA depletion provided eviden ce for enhanced DA synthesis. As in PD, the compensatory increase of D A synthesis after reserpine administration confounds the ability of CS F HVA to reflect DA depletion.