Serotonin innervation of Lurcher mutant mice: Basic data and manipulation with a combination of amantadine, thiamine and L-tryptophan

The Lurcher (Lc/+) mutant mouse is characterized by a considerable atrophy of the cerebellum due to a massive loss of cerebellar Purkinje and granule cells, as well as of neurons from the inferior olivary nucleus. In this stu dy the effects of a therapeutic combination of amantadine, thiamine and L-t ryptophan on the serotonin (5-HT) innervation was assessed in Lurcher mice by autoradiography, using [H-3]citalopram to label 5-HT transporters. In wi ld type mice as well as in both saline-treated and drug-treated Lurcher mut ants, [H-3]citalopram binding remained unchanged in forebrain and brainstem regions, In the cerebellum, labelling of deep cerebellar nuclei (CBnuc) wa s about twofold higher than in the cortex (CBctx), In saline-treated Lurche r mutants compared to wild type mice, the densities of [3H]citalopram were 98% higher in CBctx, and 180% higher in CBnuc, In CBctx of drug-treated Lur cher mutants, transporter densities were 89% higher than in the wild type, but did not differ from the saline-treated Lurcher, In the CBnuc of the dru g-treated Lurcher mutants, [3H]citalopram binding was 50% higher than in th e saline-treated Lurcher group, and 320% higher than in wild type mice, The results show that 5-HT transporters, already upregulated in the CBnuc of L urcher mutant mice, can be further increased by a pharmacological treatment , possibly altering the availability of 5-HT in some of its target areas. ( C) 1999 Elsevier Science Inc.