Tissue plasminogen activator is not involved in methamphetamine-induced neurotoxicity

J Pharmacol Sci. 2008 Feb;106(2):321-4. doi: 10.1254/jphs.sc0070328. Epub 2008 Feb 15.


To investigate the role of tissue plasminogen activator (tPA) in methamphetamine (METH)-induced dopaminergic neurotoxicity, we compared the changes in tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels in the striatum after repetitive treatment of METH at 4 mg/kg among wild-type, tPA-deficient (tPA-/-), and protease activated receptor-1-deficient (PAR-1-/-) mice. METH treatment caused a marked decrease in TH and DAT levels in the striatum of those mice with a similar magnitude. No difference in METH-induced abnormal behavior and hyperthermia was observed among the three types of mice. These results suggest that neither tPA nor PAR-1 is involved in METH-induced dopaminergic neurotoxicity in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / drug effects*
  • Corpus Striatum / metabolism
  • Dopamine Agents / toxicity*
  • Dopamine Plasma Membrane Transport Proteins / metabolism
  • Methamphetamine / toxicity*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Knockout
  • Neurotoxicity Syndromes / metabolism*
  • Nucleus Accumbens / drug effects*
  • Nucleus Accumbens / metabolism
  • Receptor, PAR-1 / genetics
  • Tissue Plasminogen Activator / genetics*
  • Tyrosine 3-Monooxygenase / metabolism


  • Dopamine Agents
  • Dopamine Plasma Membrane Transport Proteins
  • Receptor, PAR-1
  • Methamphetamine
  • Tyrosine 3-Monooxygenase
  • Tissue Plasminogen Activator