Dopamine D1 binding sites in the striatum of the mutant mouse weaver

In the weaver mouse there is a major abnormality in the dopamine-containing innervation of the striatum. Dopamine islands from 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 D1 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 D1 receptor binding sites labeled by the D1 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 Bmax 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 D1 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, D1 binding in the weaver's striatum undergoes the elaborate change in distribution of these sites that is a hallmark of normal striatal development.