Distribution of dopamine, its metabolites, and D-1 and D-2 receptors in heterozygous and homozygous weaver mutant mice

In weaver mice, besides a postnatal cerebellar developmental anomaly probab ly caused by alterations of an inwardly rectifying K+ channel, there is a p rogressive loss of mesencephalic dopaminergic neurons. To further evaluate this deficit, endogenous dopamine and its metabolites were measured in 22 b rain regions from heterozygous (wv/+) and homozygous (wv/wv) mutants, and c ompared to wild type (+/+) mice. In both wv/+ and wv/wv mutants there were profound dopamine depletions in all regions; these changes were accompanied by decreases in metabolites but with an increase of turnover indexes. Dopa mine D-1 and D-2 receptors were examined by autoradiography, and their dist ribution was conserved. The results show that the dopaminergic deficit is w idespread to all areas of innervation, and is probably compensated for by a n increased turnover. Abnormal developmental growth signals, or aberrant ce llular responses, may result in defective neurite formation of the midbrain dopaminergic neurons, leading to their postnatal death.