Milk and casein-based diets for the study of brain catecholamines in copper-deficient rats

Copper deficiency in rats results in disruption of catecholamine metabolism, the norepinephrine and dopamine concentrations in total brain being decreased in some, but not all, experiments. This study was designed to explain the discrepancies. Offspring of dams fed low copper diets (0.5 mg/kg) based on nonfat milk plus sucrose, or casein plus sucrose with and without 30% lactose, were fed the same diets until 8 wk of age. The respective control diets were supplemented with 10 mg copper/kg diet. The low copper offspring were severely deficient as indicated by liver copper levels of approximately 2 mg/kg dry weight, gross signs of enlarged and fragile hearts and neuropathological signs. On average, the dopamine concentrations in the corpus striatum of deficient rats fed milk-based diets were 70% of control values; comparable values for deficient rats fed casein-based diets were 60% of controls. Lactose had no effect on the brain pathology of copper deficiency. Approximately one-half of the deficient animals in all groups displayed low dopamine concentrations (20-50% of control values), whereas the remainder were similar to controls. Norepinephrine concentrations were consistently lower in the total brain, but actually higher in the hypothalamus of copper-deficient rats than in that of controls. Extreme variation in the norepinephrine concentrations was not observed. The high variability in the incidence of low dopamine levels suggests that another condition besides copper deficiency must be imposed to produce severe central nervous system pathology. This could be a genetic or environmental factor.