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

Abstract

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 [ 3H]SCH 23390 were studied in the striatum of 7-day and adult homozygous weaver (wv/wv) and homozygous control (+/+) mice. Saturation analysis of [ 3H]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 [ 3H]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 [ 3H]SCH 23390, are normal. The studies of regional distribution of [ 3H]SCH 23390 binding sites in 7-day and adult mice indicated that the characteristic postnatal transition of the [ 3H]SCH 23390 binding pattern from islandic to a diffuse distribution occurred normally in the weaver's caudoputamen. Thus, in spite of the degeneration and failure of development of the nigrostriatal innervation in weaver mice, D 1 binding in the weaver's striatum undergoes the elaborate change in distribution of these sites that is a hallmark of normal striatal development.