Iron deficiency alters dopamine uptake and response to L-DOPA injection in Sprague-Dawley rats.
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.
Bianco
Laura E
LE
Department of Nutritional Sciences, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Wiesinger
Jason
J
Earley
Christopher J
CJ
Jones
Byron C
BC
Beard
John L
JL
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
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