title: Running wheel exercise before a binge regimen of methamphetamine does not protect against striatal dopaminergic damage.
abstract: Repeated administration of methamphetamine (mAMPH) to rodents in a single-day "binge" dosing regimen produces long-lasting damage to forebrain dopaminergic nerve terminals as measured by decreases in tissue dopamine (DA) content and levels of the plasmalemmal DA transporter (DAT). However, the midbrain cell bodies from which the DA terminals arise survive, and previous reports show that striatal DA markers return to control levels by 12 months post-mAMPH, suggesting long-term repair or regrowth of damaged DA terminals. We previously showed that when rats engaged in voluntary aerobic exercise for 3 weeks before and 3 weeks after a binge regimen of mAMPH, exercise significantly ameliorated mAMPH-induced decreases in striatal DAT. However, these data left unresolved the question of whether exercise protected against the initial neurotoxicity from the mAMPH binge or accelerated the repair of the damaged DA terminals. The present experiments were designed to test whether exercise protects against the mAMPH-induced injury. Adult male Sprague-Dawley rats were allowed to run in wheels for 3 weeks before an acute binge regimen of mAMPH or saline, then placed into nonwheel cages for an additional week before autoradiographic determination of striatal DAT binding. The autoradiographic findings showed that prior exercise provided no protection against mAMPH-induced damage to striatal DA terminals. These results, together with analyses from our previous experiments, suggest that voluntary exercise may accelerate the repair of mAMPH-damaged DA terminals and that voluntary exercise may be useful as therapeutic adjunct in the treatment mAMPH addicts.
authors.affiliation: Department of Neurobiology and Behavior, University of California, Irvine, California, 92697.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: O'dell
authors.forename: John F
authors.initials: JF
authors.lastname: Marshall
mesh_terms: D000818:Animals; D001345:Autoradiography; D001831:Body Temperature / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000503:physiopathology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000009:adverse effects*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D012420:Running / Q000502:physiology
chemical_list: D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008694:Methamphetamine; D004298:Dopamine
keywords: DAT; [125I]RTI-55; autoradiography; dopamine; hyperthermia; neurotoxicity