Evaluation of neurotoxicity of TIQ and MPTP and of parkinsonism-preventing effect of 1-MeTIQ by in vivo measurement of pre-synaptic dopamine transporters and post-synaptic dopamine D(2) receptors in the mouse striatum

J Neurochem. 2001 Nov;79(4):868-76. doi: 10.1046/j.1471-4159.2001.00619.x.

Abstract

Parkinsonism-inducing neurotoxicity of 1,2,3,4-tetrahydroisoquinoline (TIQ), as contrasted to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and parkinsonism-preventing effect of 1-methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTIQ) have been investigated in mice by measuring their effects on the in vivo binding of radioligand to pre-synaptic dopamine transporters (DATs) or to dopamine D(2) receptors (D2R) in the striatum. A significant reduction of the ligand-DATs binding was found in the mice treated with MPTP, but not with TIQ, under the dosage inducing behavioral abnormality and loss of tyrosine hydroxylase-positive cells in the substantia nigra. A slight decrease in the ligand-DATs binding was observed in the mice given a larger dose of TIQ. Compensatory up-regulation in the post-synaptic D2Rs was found in the MPTP-treated mice. Pre-treatment with (S)-enantiomer, but not (R)-enantiomer, of 1-MeTIQ prevented the degeneration of DATs to some extent. We concluded that the TIQ-induced parkinsonism model is different from the MPTP-induced model as evaluated by the radioligand-DATs binding and that (S)-1-MeTIQ has a preventing effect for the degeneration of the DATs to a certain extent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Binding, Competitive / drug effects
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Dopamine Plasma Membrane Transport Proteins
  • Dose-Response Relationship, Drug
  • Hypokinesia / chemically induced
  • Hypokinesia / prevention & control
  • Isoquinolines / pharmacology*
  • Isoquinolines / toxicity*
  • Ligands
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins*
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / physiopathology
  • Parkinsonian Disorders / prevention & control*
  • Radioligand Assay
  • Receptors, Dopamine D2 / metabolism*
  • Stereoisomerism
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism
  • Synapses / metabolism
  • Tetrahydroisoquinolines*
  • Tyrosine 3-Monooxygenase / biosynthesis
  • Up-Regulation / drug effects

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Isoquinolines
  • Ligands
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptors, Dopamine D2
  • Tetrahydroisoquinolines
  • 1-methyl-1,2,3,4-tetrahydroisoquinoline
  • 1,2,3,4-tetrahydroisoquinoline
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase