Methamphetamine-induced neuronal damage: a possible role for free radicals

Neuropharmacology. 1989 Oct;28(10):1145-50. doi: 10.1016/0028-3908(89)90130-5.

Abstract

The hypothesis that methamphetamine-induced neuronal damage is mediated by the production of free radicals was evaluated by pretreating rats with either antioxidants or a superoxide dismutase (SOD) inhibitor. It was found that methamphetamine (dose range 6.25-25.0 mg/kg) caused long-lasting depletions of dopamine and serotonin in the striatum and that pretreatment with the antioxidants, ascorbic acid (10-100 mg/kg), ethanol (1 g/kg), mannitol (2 g/kg), or vitamin E (2 g/kg), attenuated these depletions, whereas pretreatment with the superoxide dismutase inhibitor diethyldithiocarbamate (200-400 mg/kg) exacerbated the depletions. The alteration of this effect by four different antioxidants, as well as an inhibitor of superoxidase dismutase, indicated that oxygen-free radicals may have a role in the methamphetamine-induced neurotoxicity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain Chemistry / drug effects
  • Ditiocarb / pharmacology
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Ethanol / pharmacology
  • Free Radicals
  • Male
  • Mannitol / pharmacology
  • Methamphetamine / toxicity*
  • Neurons / drug effects*
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains
  • Serotonin / metabolism
  • Superoxide Dismutase / antagonists & inhibitors
  • Vitamin E / pharmacology

Substances

  • Free Radicals
  • Vitamin E
  • Serotonin
  • Ethanol
  • Mannitol
  • Methamphetamine
  • Ditiocarb
  • Superoxide Dismutase
  • Dopamine