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Dopamine D 1 binding sites in the striatum of the mutant mouse weaver

Neuroscience, ISSN: 0306-4522, Vol: 28, Issue: 1, Page: 69-82
1989
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Article Description

In the weaver mouse there is a major abnormality in the dopamine-containing innervation of the striatum. Dopamine islands form during development, along with some innervation of the non-islandic matrix; but during the first postnatal month much of the islandic innervation degenerates and there is a failure of the normal postnatal development of the diffuse nigrostriatal innervation. In the experiments reported here we analysed the distribution of D 1 dopamine receptor-related binding sites in the weaver striatum in an effort to test the relationship between the dopamine-containing innervation of the striatum and the synthesis and distribution of dopamine receptors there. Dopamine D 1 receptor binding sites labeled by the D 1 specific antagonist [ 3 H]SCH 23390 were studied in the striatum of 7-day and adult homozygous weaver (wv/wv) and homozygous control (+/+) mice. Saturation analysis of [ 3 H]SCH 23390 binding in adult animals suggested that the dissociation constants of the binding sites are similar in mutants and controls. The B max values in the striatum of weavers were 16% higher than in the controls when the data were expressed as fmoles/mg protein. The protein content of the adult weaver's striatum was decreased by 15 to 30%, however, so that when values were expressed as fmoles/section, no significant difference between values in weavers and homozygous controls were found. Quantitative autoradiography supported the results of saturation analysis. We conclude that the apparent increase of [ 3 H]SCH23390 binding sites in the mutants occurred as the result of shrinkage of the weaver's caudoputamen and that dopamine D 1 receptor binding sites in the caudoputamen, as assessed with [ 3 H]SCH 23390, are normal.

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