title: Iron deficiency alters dopamine uptake and response to L-DOPA injection in Sprague-Dawley rats.
abstract: Iron deficiency (ID) disrupts brain dopamine (DA) and norepinephrine (NE) metabolism including functioning of monoamine transporters and receptors. We employed caudate microdialysis and no net flux (NNF) in post-weaning rats to determine if ID decreased the extraction fraction (E(d)). Five micromolar quinpirole, a dopamine D(2) receptor agonist, resulted in 80% decrease in extracellular DA and 45% higher E(d) in control animals. The D(2) agonist had no effect on E(d) in ID animals despite a reduction in basal DA. DAT mRNA levels were reduced by 58% with ID, while DAT protein in ventral midbrain and caudate and membrane associated DAT were also reduced by ID. Carbidopa/l-DOPA was administered to determine if elevated extracellular DA in ID was due to increased release. The DA response to l-DOPA in ID rats was 50% smaller and delayed, whereas the NE response was threefold higher. The caudate concentration of NE was also elevated in ID. Elevated dopamine-beta-hydroxylase activity in ID provides a tentative explanation for the increased NE response to l-DOPA. These experiments provide new evidence that ID results in altered synthesis and functioning of DAT and perhaps suggests some compensatory changes in NE metabolism.
authors: Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors: Laura E
authors: LE
authors: Bianco
authors: Jason
authors: J
authors: Wiesinger
authors: Christopher J
authors: CJ
authors: Earley
authors: Byron C
authors: BC
authors: Jones
authors: John L
authors: JL
authors: Beard
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism* / Q000503:physiopathology; D001928:Brain Diseases, Metabolic / Q000378:metabolism* / Q000503:physiopathology; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D000090463:Iron Deficiencies; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009638:Norepinephrine / Q000096:biosynthesis; D019257:Quinpirole / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D012148:Restless Legs Syndrome / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015259:Dopamine Agents; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D007980:Levodopa; D004298:Dopamine; D009638:Norepinephrine