Elevated Serotonin and Reduced Dopamine in Subregionally Divided Huntington's Disease Striatum

We measured the rostrocaudal distribution of serotonin, dopamine, and their metabolites in Huntington's disease striatum (caudate and putamen). Mean levels of serotonin or 5-hydroxyindoleacetic acid were elevated in most striatal subdivisions, whereas concentrations of dopamine or its metabolite homovanillic acid were slightly to markedly reduced. Dopamine and serotonin were at control levels in the nucleus accumbens and substantia nigra. Whereas the above-normal serotonin can most likely be accounted for by striatal atrophy, the reduced dopamine suggests either a marked down-regulation of nigrostriatal dopamine neurons or an actual reduction in the arborization of the striatal dopamine neurons. As experimental animal data suggest, the relative excess of striatal serotonin or one of its metabolites may facilitate the neurodegenerative process in Huntington's disease striatum.