title: In vivo imaging of mitochondrial function in methamphetamine-treated rats.
abstract: Abuse of the powerfully addictive psychostimulant, methamphetamine, occurs worldwide. Recent studies have suggested that methamphetamine-induced dopaminergic neurotoxicity is related to oxidative stress. In response to nerve activation, the mitochondrial respiratory chain is rapidly activated. The enhancement of mitochondrial respiratory chain activation may induce oxidative stress in the brain. However, there is little experimental evidence regarding the mitochondrial function after methamphetamine administration in vivo. Here, we evaluated whether a single administration of methamphetamine induces ATP consumption and overactivation of mitochondria. We measured mitochondrial function in two different ways: by monitoring oxygen partial pressure using an oxygen-selective electrode, and by imaging of redox reactions using a nitroxyl radical (i.e., nitroxide) coupled with Overhauser-enhanced magnetic resonance imaging (OMRI). A single administration of methamphetamine to Wistar rats induced dopaminergic nerve activation, ATP consumption and an increase in mitochondrial respiratory chain function in both the striatum and cortex. Furthermore, antioxidant TEMPOL prevented the increase in mitochondrial oxidative damage and methamphetamine-induced sensitization. These findings suggest that energy-supplying reactions after dopaminergic nerve activation are associated with oxidative stress in both the striatum and cortex, leading to abnormal behavior.
authors.affiliation: Department of REDOX Medicinal Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shiba
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yamato
authors.forename: Wataru
authors.initials: W
authors.lastname: Kudo
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hideo
authors.initials: H
authors.lastname: Utsumi
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004579:Electron Transport / Q000187:drug effects / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D000255:Adenosine Triphosphate