Effects of L-tryptophan on indoleamines and catecholamines in discrete brain regions of wild type and Lurcher mutant mice

The biochemical parameters of the serotoninergic system were examined in wi ld type mice and Lurcher mutants after chronic treatment (40 days) with the serotonin (5-MT) precursor L-tryptophan (50 mg/kg; i.p.). Tissue contents in 5-MT, dopamine and noradrenaline, as well as some of their metabolites, were measured in frontal cortex, neostriatum, thalamus, brainstem, cerebell um and spinal cord by high-performance liquid chromatography. The tissue le vels were used as a biochemical index of the function of the monoamine inne rvations in this animal model of cerebellar ataxia. The results show that L urcher mutants retain higher concentrations of L-tryptophan and total indol eamines, but that 5-HT is probably stored in a non-releasable compartment. In the particular case of the hypoplastic cerebellum, the reorganization of 5-HT nerve terminals leads to an accrued indoleamine synthesis, indicating that the Lurcher mutants can accumulate 5-MT, but do not utilize it effici ently in synaptic transmission.