Protective effects of interferon-γ against methamphetamine-induced neurotoxicity

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.