Differential effect of dietary selenium on the long-term neurotoxicity induced by MDMA in mice and rats

Neuropharmacology. 2003 Mar;44(4):449-61. doi: 10.1016/s0028-3908(02)00411-2.

Abstract

We examined the effect of dietary selenium (Se) on the long-term effect of 3,4-methylenedioxymethamphetamine (MDMA) on dopamine (DA) and 5-hydroxytryptamine (5-HT) containing neurons in the brain of mice and rats. Animals were fed either a Se-deficient (<0.02 ppm) or Se-replete (0.2 ppm) diet for 8 weeks. On the seventh week mice received three injections of MDMA (15 mg/kg, i.p. 3 h apart) or saline and rats a single dose of MDMA (12.5 mg/kg i.p.) or saline. All animals were sacrificed 7 days later. MDMA administration to mice depleted striatal DA concentration in both dietary groups, although depletion was considerably larger in the Se-deficient mice (64%) than Se-replete mice (30%). In addition, a decrease in 5-HT (17-32%) occurred in brain regions of Se-deficient but not Se-replete mice. In rats, MDMA decreased cortical [(3)H]-paroxetine binding (62%) and 5-HT content, the depletion being similar in the Se-deficient and Se-replete groups. No DA loss occurred in either group. There was no difference in the hyperthermic response induced by MDMA in Se-deficient or Se-replete animals. The Se-deficient diet decreased glutathione peroxidase (GPx) activity by 30% in mouse striatum and cortex and increased the degree of lipid peroxidation in cortical synaptosomes. Se-deficient rats also showed a decrease in brain GPx activity compared with the Se-replete group, but the degree of lipid peroxidation in synaptosomes was similar in both dietary groups. These results suggest that the antioxidant capacity of rats and mice differ leading to a differential susceptibility to the oxidative stress caused by MDMA in situations of low dietary Se.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Diet
  • Dopamine / metabolism
  • Drug Synergism
  • Eating / drug effects
  • Glutathione Peroxidase / metabolism
  • In Vitro Techniques
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • N-Methyl-3,4-methylenedioxyamphetamine / toxicity*
  • Rats
  • Selenium / administration & dosage
  • Selenium / deficiency
  • Selenium / toxicity*
  • Serotonin / metabolism
  • Species Specificity
  • Weight Gain / drug effects

Substances

  • Serotonin
  • Glutathione Peroxidase
  • Selenium
  • N-Methyl-3,4-methylenedioxyamphetamine
  • Dopamine