In vivo changes of catecholamines in hemiparkinsonian monkeys measured by microdialysis.
In monkeys, unilateral intracarotid infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces a useful model of hemiparkinsonism. To evaluate MPTP-induced neurochemical changes in vivo, brain microdialysis was employed to measure extracellular levels of dopamine and its metabolites in the neostriatum of normal and hemiparkinsonian rhesus monkeys (Macaca mulatta). The microdialysis probes were implanted bilaterally into the caudate nucleus and putamen at coordinates determined from magnetic resonance imaging. Dopamine and its metabolites were depleted in the MPTP-lesioned side versus the unlesioned side in hemiparkinsonian monkeys. Tyrosine hydroxylase immunocytochemistry revealed a complete unilateral denervation in the caudate nucleus and putamen and a total loss of tyrosine hydroxylase-immunoreactive cells in the substantia nigra pars compacta in those monkeys. Baseline levels of amines in the neostriatum in normal monkeys were not significantly different from those in the normal (non-MPTP-treated) side in hemiparkinsonian monkeys. These data demonstrate that brain microdialysis is a valuable tool for measuring in vivo neurochemical changes in nonhuman primate brains.
Skirboll
S
S
Surgical Neurology Branch, NINDS, National Institutes of Health, Bethesda, Maryland 20892.
Wang
J
J
Mefford
I
I
Hsiao
J
J
Bankiewicz
K S
KS
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002421:Caudate Nucleus / Q000378:metabolism*; D003956:Dialysis; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D010302:Parkinson Disease, Secondary / Q000378:metabolism*; D011699:Putamen / Q000378:metabolism*
D002395:Catecholamines; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; C001746:3-methoxytyramine; D004298:Dopamine; D006719:Homovanillic Acid