Neurobehavioral analysis of developmental iron deficiency in rats

Iron deficiency (ID) in early life alters the course of behavioral and cognitive development in humans, causing decreased physical activity and responsiveness to the environment. The effects of ID on behavior are similar in rats and hypothesized to be related to ID-related impairments in central dopamine pathways. The objective of this study was to examine the association between brain iron measures of dopamine function, and behavioral measures of activity and reactivity. Male and female weanling rats were fed either an iron deficient diet or control diet for 6 weeks. The iron deficient rats showed significantly decreased activity and increased anxiety-like behaviors. Iron deficient rats also showed significant decrements in brain iron content in the corpus striatum, prefrontal cortex, and midbrain and decreases in dopamine receptors and the transporter in the same areas. Multiple regression analysis showed ventral midbrain iron concentration and dopamine D(1) receptor density to be highly associated with exploration and repeated movements, respectively. In addition, the results showed anxiety-like behaviors to be related to prefrontal cortex dopamine transporter and dopamine D(1) receptor densities. We conclude from these analyses that iron concentration in dopamine containing regions and densities of dopamine receptors and the transporter, are significant predictors of measures of activity and reactivity. These observations also strengthen the argument that the Fe-dopamine link is fundamental to understanding biobehavioral difficulties seen in children with ID anemia.