Distribution of serotonin, its metabolites and 5-HT transporters in the neostriatum of Lurcher and weaver mutant mice

Abstract

Serotonin (5-HT) uptake sites, or transporters, were measured in the neostriatum (caudate putamen) of wild type (+/+) mice and heterozygous (wv/+) and homozygous (wv/wv) weaver, as well as in heterozygous Lurcher (Lc/+) mutants. These topological surveys were carried out by quantitative ligand binding autoradiography using the uptake site antagonist [ 3H]-citalopram as a probe of innervation densities in four quadrants of the rostral neostriatum and in two halves of the caudal neostriatum. In addition, tissue concentrations of 5-HT, 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophol were measured by high-performance liquid chromatography with electrochemical detection in these neostriatal divisions. In +/+ mice and in Lc/+ mutants there was a dorso-ventral gradient of increasing 5-HT levels, and they exhibited a similar heterogeneity of [ 3H]-citalopram labeling. In contrast, the gradients of 5-HT concentrations and [ 3H]-citalopram binding disappeared in the weaver mutants, suggesting a rearrangement of the 5-HT innervation. This reorganization of the 5-HT system in the neostriatum was more obvious in the wv/wv and is compatible with the hypothesis that the postnatal dopaminergic deficiencies that characterize weaver mutants lead to a sprouting of fibers and thus constitute a genetic model of dopaminergic denervation that leads to a 5-HT hyperinnervation.