Differential toxic effects of methamphetamine (METH) and methylenedioxymethamphetamine (MDMA) in multidrug-resistant (mdr1a) knockout mice

Hema Mann, Bruce Ladenheim, Hiroshi Hirata, Timothy H Moran, Jean Lud Cadet

Research output: Contribution to journalArticle

Abstract

The toxic effects of methamphetamine (METH) (2.5, 5.0 and 10.0 mg/kg) and methylenedioxymethamphetamine (MDMA) (5.0, 10.0 and 20.0 mg/kg) on dopaminergic systems were assessed in the striatum and of the nucleus accumbens in mdr1a wild-type and knockout mice. METH caused significant dose- dependent decreases of dopamine (DA) and DA transporters (DAT) in the striatum and the nucleus accumbens (NAc) of both wild-type and knockout mice. The lowest doses of METH (2.5 mg/kg) caused only small changes in the wild- type, but marked decreases in the mdr1a knockout mice. The two higher doses (5 mg/kg and 10 mg/kg) caused similar changes in both strains of mice. In contrast to METH, MDMA caused greater percentage decreases in DAT in the wild-type mice. For example, the lowest dose (5 mg/kg) caused significant decreases in DAT in the NAc of wild-type but not of mdr1a knockout mice. The highest dose (20 mg/kg) caused similar changes in both the strains. These results suggest that METH and MDMA interact differentially with P- glycoproteins. These observations document, for the first time, a role for these proteins in the entry of METH and MDMA into the brain via the blood- brain barrier, with P-glycoprotein possibly facilitating the entry of MDMA but interfering with that of METH into the brain.

Original languageEnglish (US)
Pages (from-to)340-346
Number of pages7
JournalBrain Research
Volume769
Issue number2
DOIs
Publication statusPublished - Sep 26 1997

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Keywords

  • Bloo d-brain barrier
  • Cancer
  • Dopamine
  • Methamphetamine
  • Methylenedioxymethamphetamine
  • Neurotoxicity
  • Nucleus accumbens
  • P- glycoprotein
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

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