Dopamine transporter knock-out mice are hypersensitive to 3-nitropropionic acid-induced striatal damage

Eur J Neurosci. 2002 Jun;15(12):2053-6. doi: 10.1046/j.1460-9568.2002.02047.x.

Abstract

Evidence suggests that dopamine is involved in the modulation of striatal excitotoxic processes. To further investigate this issue, we studied the effects of systemic 'low-dose' (total dose, 340 mg/kg in 7 days) 3-nitropropionic acid (3-NP) intoxication in dopamine transporter knock-out mice (DAT-/-) compared to wildtype (DAT+/+) mice. Systemic 'low-dose' 3-NP induced a significant impairment in a rotarod task only in DAT-/- mice. Histopathology also demonstrated a significant reduction of the striatal volume (-7%, P < 0.05), neuronal density (-12.5%, P < 0.001) and absolute number estimates of striatal neurons (-11.5%, P < 0.001) in DAT-/- compared to DAT+/+ mice, with increased glial activation, independent of the degree of succinate dehydrogenase inhibition. These findings strengthen the hypothesis for dopamine modulation of excitotoxicity within the nigrostriatal system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basal Ganglia Diseases / chemically induced
  • Basal Ganglia Diseases / metabolism*
  • Basal Ganglia Diseases / physiopathology
  • Cell Death / drug effects
  • Cell Death / physiology
  • Convulsants / pharmacology
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Dose-Response Relationship, Drug
  • Drug Tolerance / genetics*
  • Membrane Glycoproteins*
  • Membrane Transport Proteins / deficiency*
  • Membrane Transport Proteins / genetics
  • Mice
  • Mice, Knockout
  • Motor Activity / drug effects
  • Motor Activity / genetics
  • Neostriatum / injuries
  • Neostriatum / metabolism*
  • Neostriatum / physiopathology
  • Nerve Degeneration / chemically induced
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Nerve Tissue Proteins*
  • Neural Pathways / injuries
  • Neural Pathways / metabolism*
  • Neural Pathways / physiopathology
  • Neurotoxins / pharmacology
  • Nitro Compounds
  • Postural Balance / drug effects
  • Postural Balance / physiology
  • Propionates / pharmacology
  • Substantia Nigra / injuries
  • Substantia Nigra / metabolism*
  • Substantia Nigra / physiopathology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Convulsants
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Neurotoxins
  • Nitro Compounds
  • Propionates
  • Slc6a3 protein, mouse
  • 3-nitropropionic acid
  • Dopamine