Age-dependent effects of gestational and lactational iron deficiency on anxiety behavior in rats

Gestational iron deficiency (ID) has been linked to alterations in GABA neurotransmission, but whether these neuronal changes are mirrored in altered anxiety behavior in rats is not known. In this experiment, two tests of GABA-related affective behaviors in rats, ultrasonic vocalizations (USVs) and elevated plus maze (EPM) were used to investigate the consequences of maternal ID. Female rats were randomly assigned to one of three diet groups: low iron (10-20 ppm Fe), recommended (standard) iron control (60 ppm Fe) or lab chow (250 ppm Fe) control. Diets started 7 days prior to mating and continued until 10 days after birth (PN10). Maternal behavior and offspring growth and activity were also assessed. Blood samples taken on PN10 revealed a significant decrement in serum iron and an increase in total iron binding capacity in the low iron groups compared to the two control groups. Relative to the two control groups, the low iron group weighed less on PN1, and this weight difference persisted in adulthood. In neonates, the rate of USVs in the low iron group was significantly higher than the two control groups, and their general activity was significantly less than the controls. Maternal behavior was not significantly different across groups. By adulthood, anxiety behavior and motor activity in the low iron group were comparable to controls, although the iron deficient subjects habituated more slowly. This study shows that prenatal iron deficiency results in increased anxiety behavior in neonates that appears to be reversed with iron repletion but that some aspects of altered exploratory behavior and growth persist into adulthood.