PROGRESSIVE ACCUMBENS DEGENERATION AFTER NEONATAL STRIATAL 6-HYDROXYDOPAMINE IN RATS

Parkinson's disease is associated with progressive loss of nigrostriat al 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 ip silateral 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 incr eased in ipsilateral accumbens, and may yield tissue-damaging neurotox ic by-products. This paradigm may help in elucidating mechanisms respo nsible for gradual degeneration of DA neurons and for screening potent ial neuroprotective agents. (C) 1998 Elsevier Science Ireland Ltd.