Noradrenaline depletion exacerbates MPTP-induced striatal dopamine loss in mice

Eur J Pharmacol. 1993 Jun 4;236(3):487-9. doi: 10.1016/0014-2999(93)90489-5.

Abstract

Injection of C57Bl/6 mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 4 x 10 mg/kg i.p. over 8 h) resulted in a partial (40%) striatal dopamine depletion at 7 days post-drug. Pretreatment with the selective noradrenergic neurotoxin N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine (DSP-4; 40 mg/kg i.p.), while having no effect per se on striatal dopamine levels, exacerbated the MPTP-induced dopamine deficit to 60%. Results support the hypothesis that damage to the locus coeruleus-noradrenergic system, by removing a facilitatory influence on the nigrostriatal dopamine system, interferes with the ability of the nigrostriatal pathway to compensate for or recover from injury.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / metabolism
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Adrenergic Agents / pharmacology*
  • Animals
  • Benzylamines / toxicity*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Injections, Intraperitoneal
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Norepinephrine / metabolism*

Substances

  • Adrenergic Agents
  • Benzylamines
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • DSP 4
  • Dopamine
  • Norepinephrine