Progressive accumbens degeneration after neonatal striatal 6-hydroxydopamine in rats.
Parkinson's disease is associated with progressive loss of nigrostriatal dopamine (DA). Models of the disorder, produced with neurotoxins (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 6-hydroxydopamine) that selectively lesion DA neurons, are characterized by acute removal and gradual recovery of DA. We report slowly progressive loss of DA in ipsilateral nucleus accumbens following profound (>90%) acute unilateral depletion of DA in the caudate-putamen of neonatal rats, from 50% at age 27 days to 94% by 100 days. Metabolic turnover of DA markedly increased in ipsilateral accumbens, and may yield tissue-damaging neurotoxic by-products. This paradigm may help in elucidating mechanisms responsible for gradual degeneration of DA neurons and for screening potential neuroprotective agents.
Teicher
M H
MH
Consolidated Department of Psychiatry and Neuroscience Program, Harvard Medical School, Boston, MA, USA.
Andersen
S L
SL
Campbell
A
A
Gelbard
H A
HA
Baldessarini
R J
RJ
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D000831:Animals, Newborn; D002421:Caudate Nucleus / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D004298:Dopamine / Q000502:physiology; D006719:Homovanillic Acid / Q000032:analysis; D009410:Nerve Degeneration / Q000139:chemically induced*; D009498:Neurotoxins / Q000633:toxicity*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000473:pathology; D016627:Oxidopamine / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology; D011699:Putamen / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D004298:Dopamine; D006719:Homovanillic Acid