Alpha-1b adrenergic receptor knockout mice are protected against methamphetamine toxicity

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The psychostimulant methamphetamine (MA) is toxic to nigrostriatal dopaminergic terminals in both experimental animals and humans. In mice, three consecutive injections of MA (5 mg/kg, i.p. with 2 h of interval) induced a massive degeneration of the nigro-striatal pathway, as reflected by a 50% reduction in the striatal levels of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC), by a substantial reduction in striatal tyrosine hydroxylase and high-affinity DA transporter immunostaining, and by the development of reactive gliosis. MA-induced nigro-striatal degeneration was largely attenuated in mice lacking α1b-adrenergic receptors (ARs). MA-stimulated striatal DA release (measured by microdialysis in freely moving animals) and locomotor activity were also reduced in α1b-AR knockout mice. Pharmacological blockade of α-adrenergic receptors with prazosin also protected wild-type mice against MA toxicity. These results suggests that α1b-ARs may play a role in the toxicity of MA on nigro-striatal DA neurons.

Original languageEnglish
Pages (from-to)413-421
Number of pages9
JournalJournal of Neurochemistry
Issue number2
Publication statusPublished - Jul 2003


  • α1-adrenergic receptor antagonists
  • Methamphetamine neurotoxicity
  • Parkinson's disease

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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