Behavioral and biochemical effects of L-tryptophan and buspirone in a model of cerebellar atrophy

The Lurcher mutant mouse can be considered an adequate model of autosomal d ominant spinocerebellar atrophy because of the severe degeneration of its c erebellar cortex and inferior olive. The purpose of this study was to deter mine whether the motor coordination deficits of Lurcher mutants could be im proved after chronic administration of the serotonin (5-hydroxytryptamine; 5-HT) precursor, L-tryptophan, or of the 5-HT1A agonist, buspirone. During these treatments, the mice were submitted to behavioral evaluations using t he coat hanger and the rotorod tests, as well as an inclined screen and a v ertical grid test. At the end of treatments, 5-HT and 5-hydroxindole-3-acet ic acid (5-HIAA) were measured in six brain regions. On the coat hanger tes t, administration Of L-tryptophan accelerated movements along the horizonta l bar by 44%, while buspirone increased the time spent on the apparatus by 11%. Neither drug had an effect on climbing ability or on the time spent on a rotating beam. Administration of L-tryptophan increased 5-HIAA levels in frontal cortex, neostriatum, thalamus, brainstem, cerebellum and spinal co rd, but elevated 5-HT only in neostriatum, brainstem and cerebellum. In con trast, buspirone led to 5-HT increases in cerebellum and augmented 5-HIAA i n the spinal cord. The modest test-specific improvements are consistent wit h some of the clinical data concerning 5-HT pharmacotherapy in patients suf fering from cerebellar atrophy. (C) 2001 Elsevier Science Inc. All rights r eserved.