Abstract
The compound 6-hydroxydopamine (6-OHDA) was the first neurotoxin documented to produce long-term depletion and destruction of norepinephrine in peripheral sympathetic neurons without affecting central catecholamine content (1–3). Subsequently, it was found that this neurotoxic compound would produce a selective destruction of brain catecholamine-containing neurons if administered directly into brain (4–7). In addition to the use of 6-OHDA, the discovery and development of a second compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which selectively destroys central dopaminergic neurons, will be reviewed (8,9). The various techniques utilized to provide effective lesions of catecholamine-containing neurons with these neurotoxins will be described (see 10,11), as well as how the use of these neurotoxic compounds has made significant contributions to our knowledge of the structural organization, physiological role, and neural mechanisms of central catecholamine-containing systems. Recently initiated work to investigate the action and role of neurotrophic factors in relation to the growth, maintenance, and recovery of central catecholamine-containing neurons after neurotoxin treatment will be examined. Subsequently, we will review how these neurotoxin treatments are being used to model two clinical disorders with neuropathology to dopamine-containing systems in brain, parkinsonism and Lesch-Nyhan disease. Finally, we will describe the various efforts undertaken with the neurotoxin-treated animals to enhance dopaminergic function in vivo and the application of these results to the restoration of dopaminergic function in Parkinson’s patients.
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Breese, C.R., Breese, G.R. (1998). The Use of Neurotoxins to Lesion Catecholamine-Containing Neurons to Model Clinical Disorders. In: Kostrzewa, R.M. (eds) Highly Selective Neurotoxins. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-477-1_2
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