Effects of Depleted Uranium on Mouse Midbrain Catecholamines and Related Behavior

Abstract

Depleted uranium (DU) has been shown to have a variety of neurophysiologic effects. Humans demonstrate differences in cognitive testing and serum prolactin levels. Animals exposed to DU demonstrate changes in neurochemistry, development, and behavior. Because catecholamines mediate a number of behaviors we sought to determine if DU affects catecholamine metabolism and related behaviors. Mice were exposed to DU at 0 or 75mg/L in water for 2 weeks. Afterwards the animals were tested in an open-field apparatus. Two days later the animals from each group were injected with apomorphine (10mg/kg) or normal saline and tested again in the open-field. Afterwards, the midbrain concentrations of dopamine, tyrosine, 3,4dihydroxyphenylalanine (DOPA), norepinephrine, epinephrine, and homovanillic acid were determined by HPLC. We found that DU elevates midbrain tyrosine levels while decreasing DOPA, norepinephrine and epinephrine levels. Dopamine and homovanillic acid levels were unaffected. Previous studies have shown that DU increases brain lipid peroxidation which is correlated with behavioral changes. To determine if lipid peroxidation was related to changes in catecholamines lipidperoxidation was measured using the thiobarbituric acid method. We found that open-field activity and lipid peroxidation increased with DU exposure. No relationship was found between lipid peroxidation and any of the catecholamine related substances. Lastly, DU exposure did not significantly influence the behavior of mice when challenged with the dopamine agonist apomorphine.