Iron deficiency alters dopamine transporter functioning in rat striatum

Iron deficiency anemia in early life produces profound changes in both in v ivo and in vitro evaluations of dopamine (DA) functioning. This study emplo yed both behavioral and biochemical approaches to examine the biological ba ses of alterations in striatal DA metabolism seen in iron-deficient rats. T he purpose was to determine whether the DA transporter (DAT) was functional ly 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 behavior al testing. Motor activity responses to graded doses (3.75-30 mg/kg body) o f the DA uptake inhibitor, cocaine, were significantly blunted in iron-defi cient rats with a 50% higher half-maximal effective dose (ED50) in both mal es 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). Radioligan d binding assays with H-3-1-(2- (diphenylmethoxy)-ethyl)-4-(3-phenylpropyl) piperazine (H-3-GBR12935) demonstrated that iron deficiency did not alter the affinity of the ligand for the DAT but did significantly decrease the d ensity of the transporter by 30% in caudate putamen and 20% in nucleus accu mbens. Iron deficiency also significantly decreased H-3-DA uptake into stri atal synaptosomes, but did not affect release of DA with potassium chloride stimulation. These experiments provide supporting evidence that elevated l evels 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 re lease.