ABSTRACT
ABSTRACT Concentrations of 5HT increased in the cerebellum and brainstem of Nna1pcd-1J (Purkinje cell degeneration) mutant mice. Increased cerebellar 5HT concentrations were also found in Grid2Lc
(Lurcher), Grid2ho (hot-foot), Rorasg (staggerer), and Girk2Wv (Weaver) mutant mice with cerebellar atrophy. In a similar fashion, increased levels of 5-hydroxyindoleacetic acid (5HIAA), the main 5HT metabolite, were reported in the cerebrospinal uid of patients with spinocerebellar atrophy. Based on the hypothesis of insufcient neurotransmission, pharmacotherapy with the 5HT precursors 5-hydroxytryptophan (5HTP) and tryptophan improved motor coordination in patients or mice with cerebellar atrophy, respectively. 5HT-related therapy has also been successful in other neurological conditions such as akinesia, tardive dyskinesia, and spinal trauma. Tardive dyskinesia can be counteracted by substances that potentiate the 5HT synapse, such as 5HTP, citalopram, uoxetine, and paroxetine. Likewise, spinal trauma can be counteracted by 5HT and 5HTP as well as 5HT receptor agonists.
