Learning deficits and brain monoamines in rats with congenital hyperbilirubinemia

At 28 days of age, rats with congenital hyperbilirubinemia (homozygous Gunn strain) were submitted to an active learning task (two-way shuttlebox avoidance) and a passive learning task (step-down avoidance) and the results compared with controls (heterozygous littermates). Jump thresholds to painful footshock were used as measures of pain sensitivity. After testing, the concentration of dopamine and norepinephrine was measured in eight brain regions. The jaundiced Gunn rat demonstrated significant learning retardation on both avoidance tasks compared with their controls. Because jump thresholds to shock were similar in hyperbilirubinemic animals and their controls, these differences in learning performance could not be attributed to differences in sensitivity to footshock. Norepinephrine concentrations in hypothalamus and hippocampus were elevated in jaundiced rats compared with controls. In jaundiced rats, dopamine concentrations in striatum and pons-medulla were diminished. Cerebella in jaundiced rats were significantly smaller, and total content of both dopamine and norepinephrine significantly lower in jaundiced rats compared with controls. Learning deficits in young jaundiced Gunn rats may be associated with the changes in brain catecholamine concentrations found in these animals. To determine whether or not any recovery from hyperbilirubinemia occurs, similar behavioral and biochemical testing could be applied to homozygous Gunn rats at different stages in development.