Iron deficiency alters dopamine transporter functioning in rat striatum.
Iron deficiency anemia in early life produces profound changes in both in vivo and in vitro evaluations of dopamine (DA) functioning. This study employed both behavioral and biochemical approaches to examine the biological bases of alterations in striatal DA metabolism seen in iron-deficient rats. The purpose was to determine whether the DA transporter (DAT) was functionally altered in postweaning iron deficiency. Male and female 21-d-old Sprague-Dawley rats (n = 40) were fed either an iron-deficient (ID) diet (3 mg Fe/kg diet) or a control (CN) diet (35 mg Fe/kg diet) for 4 wk before behavioral testing. Motor activity responses to graded doses (3.75-30 mg/kg body) of the DA uptake inhibitor, cocaine, were significantly blunted in iron-deficient rats with a 50% higher half-maximal effective dose (ED(50)) in both males and females (CN-female, 7.1 +/- 0.9 mg/kg; ID-female, 11.2 +/-1.3 mg/kg; CN-male, 12.0 +/- 0.7 mg/kg; and ID-male, 17.0 +/- 1.8 mg/kg). Radioligand binding assays with (3)H-1-(2-(diphenylmethoxy)-ethyl)-4-(3-phenylpropyl) piperazine ((3)H-GBR12935) demonstrated that iron deficiency did not alter the affinity of the ligand for the DAT but did significantly decrease the density of the transporter by 30% in caudate putamen and 20% in nucleus accumbens. Iron deficiency also significantly decreased (3)H-DA uptake into striatal synaptosomes, but did not affect release of DA with potassium chloride stimulation. These experiments provide supporting evidence that elevated levels of extracellular DA in the striatum of iron-deficient rats is likely to be the result of decreased DAT functioning and not increased rates of release.
Erikson
K M
KM
Graduate Program in Nutrition, Biobehavioral Health, The Pennsylvania State University, University Park, PA 16802, USA.
Jones
B C
BC
Beard
J L
JL
D000704:Analysis of Variance; D018798:Anemia, Iron-Deficiency / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004032:Diet; D004298:Dopamine / Q000378:metabolism* / Q000493:pharmacokinetics; D050483:Dopamine Plasma Membrane Transport Proteins; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins; D010879:Piperazines / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C493216:Slc6a3 protein, rat; D011189:Potassium Chloride; C044630:1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine; D003042:Cocaine; D004298:Dopamine