Protective effects of interferon-γ against methamphetamine-induced neurotoxicity

Hiroaki Hozumi, Masato Asanuma, Ikuko Miyazaki, Saki Fukuoka, Yuri Kikkawa, Naotaka Kimoto, Yoshihisa Kitamura, Toshiaki Sendo, Taizo Kita, Yutaka Gomita

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22 Citations (Scopus)

Abstract

Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-γ (IFN-γ) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-γ before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-γ before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-γ injection had no effect on METH-induced hyperthermia. In addition, IFN-γ injected centrally after METH treatment, but not systemically, 1 h after the final METH injection significantly protected against METH-induced neurotoxicity. Our results suggest that IFN-γ injected systemically or its related molecule protects against METH-induced neurotoxicity through intracerebral molecular pathways, while it can prevent METH-induced hyperthermia through different molecular events.

Original languageEnglish
Pages (from-to)123-129
Number of pages7
JournalToxicology Letters
Volume177
Issue number2
DOIs
Publication statusPublished - Mar 15 2008

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Keywords

  • Dopamine transporter
  • Hyperthermia
  • Interferon-γ
  • Methamphetamine
  • Neuroprotection
  • Neurotoxicity

ASJC Scopus subject areas

  • Toxicology

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