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

Serotonin (5-HT) uptake sites. or transporters, were measured in the neostr iatum (caudate putamen) of wild type (+/+) mice and heterozygous (wv/+) and homozygous (wv/wv) weaver, as well as in heterozygous Lurcher (Lc/+) mutan ts. These topological surveys were carried out by quantitative ligand bindi ng autoradiography using the uptake site antagonist [H-3]-citalopram as a p robe of innervation densities in four quadrants of the rostral neostriatum and in two halves of the caudal neostriatum. In addition, tissue concentrat ions of 5-HT, 5-hydroxyindole-3-acetic acid and 5-hydroxytryptophol were me asured by high-performance liquid chromatography with electrochemical detec tion 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 [H-3]-citalopram labeling. In contrast, the grad ients of 5-HT concentrations and [H-3]-citalopram binding disappeared in th e weaver mutants, suggesting a rearrangement of the 5-HT innervation. This reorganization of the 5-HT system in the neostriatum was more obvious in th e wv/wv and is compatible with the hypothesis that the postnatal dopaminerg ic deficiencies that characterize weaver mutants lead to a sprouting of fib ers and thus constitute a genetic model of dopaminergic denervation that le ads to a 5-HT hyperinnervation. (C) 2001 Elsevier Science Ltd. All rights r eserved.