Abstract
Copper-loading was produced in rats by administration of 0.125% CuSO 4 in the drinking water for a period of 11 months from weaning. At conclusion of the treatment the animals had significant increases in liver (552%) and brain (26%) copper content relative to age-matched controls. Whereas the concentration of dopamine was unaffected, the concentration of 3,4-dihydroxyphenylacetic acid in the corpus striatum was found to be lower (25% decrease) in the copper-treated group. Saturation studies of the striatal D-2 dopamine receptors using [ 3H]spiperone indicated that in copper-loaded animals the affinity was significantly increased threefold, whereas there was a trend for the number of receptors to decrease. When included in the radioligand binding assay, copper salts (Cu 2+) inhibited specific [ 3H]spiperone binding to untreated corpora striata. The inhibition produced by copper was competitive with a significant decrease in affinity, the 50% effective concentration of Cu 2+ was 21 to 24 μ M, and the potency of dopamine agonists was also decreased. These results are discussed in relation to the mechanism by which copper affects dopaminergic function and to the use of copper-loaded rats as a model of Wilson's disease.
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