Striatal extracellular dopamine levels and behavioural reversal in MPTP-lesioned mice

Neuroreport. 2009 Mar 25;20(5):482-6. doi: 10.1097/WNR.0b013e32832984d6.

Abstract

Intoxication induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in mice results in a significant loss of nigrostriatal dopamine (DA) neurons. This is accompanied by a change in behavioural phenotype that can be reversed by L-DOPA (3,4-dihydroxy-L-phenylalanine) treatment. Here, we examined the extracellular levels of DA, behavioural deficits and the response to L-DOPA treatment in severely intoxicated mice. The MPTP intoxication produced more than a 90% reduction in tissue DA and a 65% decline in extracellular DA levels. In-vivo binding did not show any increased raclopride binding to the D2 receptor. Administration of L-DOPA, 5 or 20 mg/kg (subcutaneously), significantly increased dialysate DA levels and both doses of L-DOPA reversed the behavioural deficit. Interestingly, only 5 mg/kg L-DOPA normalized DA levels to 56% of controls showing that only a minor increase in DA levels is sufficient to yield motor recovery.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism*
  • Dopamine Agents / administration & dosage
  • Extracellular Space / metabolism*
  • Levodopa / administration & dosage
  • MPTP Poisoning / drug therapy
  • MPTP Poisoning / physiopathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Neurotoxins / toxicity
  • Raclopride / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Tritium / metabolism

Substances

  • Dopamine Agents
  • Neurotoxins
  • Receptors, Dopamine D2
  • Tritium
  • Raclopride
  • Levodopa
  • Dopamine