Progressive accumbens degeneration after neonatal striatal 6-hydroxydopamine in rats

doi:10.1016/S0304-3940(98)00281-X

Neuroscience Letters

Volume 247, Issues 2–3, 15 May 1998, Pages 99-102

https://doi.org/10.1016/S0304-3940(98)00281-X Get rights and content

Abstract

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.

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Acknowledgements

Supported in part by NIH grants MH-43473 (MHT); MH-34006 and MH-47370, an award from the Bruce J. Anderson Foundation and the McLean Private Donors Fund for Neuropharmacology Research (to RJB).

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Rather, depletions that were performed under the identical situations can range from no depletion to a significant loss of dopamine. We have previously observed that an initial 6-OHDA lesion in the striatum progressively spread into a loss of dopamine in the nucleus accumbens with further maturation (Teicher et al., 1998). The same phenomenon may have occurred here with spreading from the plPFC to the ilPFC.
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The position of rats, the depth, and angle of the inserted needle and the recognition of a perforation of the dura mater were all important for appropriate CSF sampling (Huang et al., 1996; Hudson et al., 1994). DA concentration of 6-OHDA lesioned striatum and the CSF has also been examined by certain other authors (Ben et al., 1999; Espino et al., 1995; Teicher et al., 1998; van der Vegt et al., 2003). The data in our study are essentially in correlation with these previously reported findings.
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¹: Present address: Department of Pediatric Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.

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Progressive accumbens degeneration after neonatal striatal 6-hydroxydopamine in rats

Abstract

Section snippets

Acknowledgements

Eur. J. Pharmacol.

Neuroscience

Neurosci. Lett.

Biochem. Pharmacol.

FEBS Lett.

Life Sci.

Enhanced hydroxyl radical generation by 2′-methyl analog of MPTP: suppression by clorgyline and deprenyl

Synapse

The relevance of the Lewy body to the pathogenesis of idiopathic Parkinson's disease

J. Neurol. Neurosurg. Psychiatry

Relatively high levels of dopamine in nucleus accumbens of levodopa treated patients with Parkinson's disease

J. Neural Transm.

Reactive dopamine metabolites and neurotoxicity: implications for Parkinson's disease

Adv. Exp. Med. Biol.