1-Methyl-4(2′-methylphenyl)-1,2,3,6-tetrahydropyridine (2′CH3-MPTP)-induced degeneration of mesostriatal dopaminergic neurons in the mouse: biochemical and neuroanatomical studies

Kebreten F. Manaye, Patricia K. Sonsalla, Gary Barnett, Richard E. Heikkila, Donald J. Woodward, Wade K. Smith, Dwight C. German

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14 Scopus citations

Abstract

The neurotoxic effects of 1-methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydropyridine (2′CH3-MPTP), a substituted analog of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, were studied in BALB/cJ mice. Moderate doses of 2′CH3-MPTP produced a greater depletion of dopamine (DA) in the striatum (45%) than in the nucleus accumbens (23%), and in these same animals, there was a 35% loss of midbrain DA neurons. The greatest loss of DA cells occurred within the substantia nigra (43%), and there was also a significant loss of cells within the ventral tegmental area (28%). Higher doses of 2′CH3-MPTP decreased levels of DA more in the axon terminal/forebrain region (72%) than in the cell body/midbrain region (25%). Similar forebrain/midbrain DA depletion ratios were also found in mice that received an electrolytic lesion of the midbrain DA neurons; there was a greater DA depletion in the forebrain (29%) than in the midbrain (8%). In both 2′CH3-MPTP and electrolytically lesioned animals there was a significant increase in DA turnover in the forebrain region, as measured by the homovanillic acid/DA ratio. These data indicate that 2′CH3-MPTP: (1) destroys DA neurons within two midbrain regions containing cells which project to the striatum (i.e. mesostriatal DA neurons), rather than just nigrostriatal DA neurons; (2) produces a greater loss of DA in the axon terminal region than in the cell body region; and (3) influences the mesostriatal DA neurons in the same way as does a lesion to the cell bodies. These data are discussed with regard to the pathophysiology of 2′CH3-MPTP.

Original languageEnglish (US)
Pages (from-to)307-315
Number of pages9
JournalBrain Research
Volume491
Issue number2
DOIs
StatePublished - Jul 10 1989

Keywords

  • 1-Methyl-4-(2′-methylphenyl)-1,2,3,6-tetrahydropyridine
  • Midbrain dopaminergic neuron
  • Mouse
  • Nucleus accumbens
  • Striatum
  • Tyrosine hydroxylase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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