An in vivo comparison of the capacity of striatal versus extrastriatal brain regions to form dopamine from exogenously administered L-dopa.
We used the technique of cerebral microdialysis to monitor the metabolism of exogenously administered L-dopa and compared dopamine and dopamine metabolite formation in the striatum (a site containing abundant dopamine nerve terminals and dopa-decarboxylase (DDC) activity) versus the cerebellum and occipital cortex (sites with limited dopaminergic innervation and DDC activity). The concentrations of dopamine and the major dopamine metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) increased in each brain region following L-dopa perfusion; however, dopamine formation was 90% less in the occipital cortex as compared to the striatum and 95% less in the cerebellum. DOPAC formation was 57% less in the occipital cortex and 74% less in the cerebellum. HVA formation was 42% less in the occipital cortex and 70% less in the cerebellum. The levels of the L-dopa metabolite 3-O-methyldopa and the serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA) were identical in the striatum, occipital cortex, and cerebellum both before and after L-dopa administration. We conclude that brain areas with marked reductions in dopamine nerve terminals and DDC activity have a diminished capacity to synthesize dopamine and also lack storage mechanisms to protect the newly synthesized dopamine from degradative metabolism. The relevance of these findings to the use of L-dopa in treating Parkinson's disease is discussed.
Brannan
T
T
Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA.
Prikhojan
A
A
Yahr
M D
MD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001711:Biotransformation; D001923:Brain Chemistry / Q000502:physiology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000096:biosynthesis*; D015259:Dopamine Agents / Q000493:pharmacokinetics*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007980:Levodopa / Q000493:pharmacokinetics*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000378:metabolism*; D009778:Occipital Lobe / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D014443:Tyrosine; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; C008404:3-methoxytyrosine; D004298:Dopamine