Recovery by NO of the iron-attenuated dopamine dynamics in nigrostriatal system of rat brain.
In vivo electrochemical detection was employed to study the chronic effect of nitric oxide on iron-induced alterations in dopamine dynamics, including K+ -evoked dopamine overflows and the clearance of exogenous dopamine in rat striatum. Intranigral infusion of fresh S-nitroso-N-acetylpenicillamine (SNAP), a nitric oxide donor, did not alter either dopamine dynamics in the striatum or the lipid peroxidation in substantia nigra 7 days after the infusion, indicating that nitric oxide is not neurodestructive. By contrast, infusion of iron in substantia nigra chronically degenerated the nigrostriatal dopaminergic system. Co-infusion of iron and fresh SNAP, but not aged SNAP, prevented the iron-induced reductions in K+ -evoked dopamine overflows. Furthermore, the clearance of exogenous dopamine was attenuated in the striatum ipsilateral to the substantia nigra infused with iron. An improvement by fresh SNAP of iron-induced reduction in dopamine clearance was observed in rats co-infused with fresh SNAP and iron mixture compared to iron-lesioned group. Taken together, our in vivo electrochemical study suggests that nitric oxide does not alter dopamine dynamics in nigrostriatal dopaminergic system. Rather, nitric oxide appears to protect dopamine dynamics from iron-induced oxidative stress in rat brain.
Lin
A M
AM
Department of Medical Education and Research, Veterans General Hospital-Taipei, Taiwan, ROC. myalin@vghtpe.gov.tw
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000502:physiology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D018384:Oxidative Stress; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D007501:Iron; D010396:Penicillamine; D011188:Potassium; D004298:Dopamine