Subject(s)
Antiparkinson Agents/pharmacology , Endoplasmic Reticulum Stress/drug effects , Endoplasmic Reticulum/drug effects , Ergolines/pharmacology , Parkinson Disease, Secondary/metabolism , Substantia Nigra/drug effects , Animals , Cabergoline , Caspase 12/metabolism , Endoplasmic Reticulum/metabolism , Male , Mice , Mice, Inbred ICR , Oligopeptides/metabolism , Oxidopamine , Substantia Nigra/metabolism , Transcription Factor CHOP/metabolismABSTRACT
Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-gamma (IFN-gamma) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-gamma before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-gamma before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-gamma injection had no effect on METH-induced hyperthermia. In addition, IFN-gamma injected centrally after METH treatment, but not systemically, 1h after the final METH injection significantly protected against METH-induced neurotoxicity. Our results suggest that IFN-gamma 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.
