Tissue plasminogen activator is not involved in methamphetamine-induced neurotoxicity.
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.
Fukakusa
Ayumi
A
Laboratory of Neuropsychopharmacology, Graduate School of Natural Science and Technology, Kanazawa University, Japan.
Mizoguchi
Hiroyuki
H
Koike
Hiroyuki
H
Nabeshima
Toshitaka
T
Takuma
Kazuhiro
K
Yamada
Kiyofumi
K
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015259:Dopamine Agents / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D020258:Neurotoxicity Syndromes / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000235:genetics; D010959:Tissue Plasminogen Activator / Q000235:genetics*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D044463:Receptor, PAR-1; D008694:Methamphetamine; D014446:Tyrosine 3-Monooxygenase; D010959:Tissue Plasminogen Activator