Normalization of brain serotonin by L-tryptophan in levodopa-treated rats

To test possible biochemical mechanisms by which L-tryptophan may reverse mental side effects of levodopa therapy in parkinsonism we administered levodopa, 250 mg per kilogram intraperitoneally, alone and with L-tryptophan, 500 mg per kilogram intraperitoneally, to rats pretreated with the peripheral dopa decarboxylase inhibitor, carbidopa (25 mg per kilogram). Rats were decapitated 0.5, 1, and 2 hours following amino acid injection and brain levels of amino acids, amines, and acid metabolites were determined. As expected, levodopa alone reduced tryptophan and serotonin and increased dopa and dopamine at the 1 and 2 hour intervals. Concurrent administration of L-tryptophan did not significantly alter the increased dopa and dopamine but did restore serotonin levels to within normal range at all time points. If similar events occur in parkinsonian patients, normalization of brain serotonin and not competitive reduction of brain dopa and dopamine may be the basis for the improvement in mental status.