Altered nitric oxide production in mouse brain after administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridin or methamphetamine

Neurochem Int. 2004 Jun;44(8):641-6. doi: 10.1016/j.neuint.2003.09.003.

Abstract

Several studies have demonstrated the involvement of reactive nitrogen and oxygen species (RNOS) in the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridin (MPTP) and methamphetamine (METH), so the contribution of altered nitric oxide synthase (NOS) enzyme function can be suspected. In this study, about 50% increase in nitric oxide (NO) production in the mouse striatum was found between 4 and 12 h after a single MPTP injection, allowing an increased peroxynitrite (ONOO-) formation in the target brain region. However, METH injection induced a rapid decrease of NO formation both in mouse striatum and hippocampus, reaching its minimum level at 2 h, and restored to the control value after 6 h in the striatum and 12 h in the hippocampus. The uncoupled function of NOS with increased superoxide (O2*-) production after METH injection is suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / pharmacology*
  • Animals
  • Brain / enzymology
  • Brain Chemistry / drug effects*
  • Central Nervous System Stimulants / toxicity*
  • Dopamine Agents / toxicity*
  • Hippocampus / drug effects
  • Hippocampus / enzymology
  • Injections, Intraperitoneal
  • Male
  • Methamphetamine / toxicity*
  • Mice
  • Neostriatum / drug effects
  • Neostriatum / enzymology
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase Type I
  • Peroxynitrous Acid / metabolism

Substances

  • Central Nervous System Stimulants
  • Dopamine Agents
  • Peroxynitrous Acid
  • Nitric Oxide
  • Methamphetamine
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse