Influence of plasma tryptophan on brain 5HT synthesis and serotonergic activity.

Studies are described on the effect of plasma tryptophan changes on brain 5HT synthesis in man and rat. Results show that human brain 5HT synthesis is influenced by the supply of tryptophan to the brain. This is indicated by: (a) significant correlations between plasma free tryptophan and CSF 5HIAA concentrations; (b) raised cortical 5HT concentrations after infusing tryptophan. In rat experiments, determinations of brain tryptophan uptake from a bolus of plasma injected into the carotid artery showed: (a) increased uptake when bolus free tryptophan was raised and total tryptophan kept constant; (b) unchanged uptake when bolus free tryptophan was kept constant and total tryptophan decreased. Brain tryptophan uptake from a buffer bolus was decreased by large neutral amino acids. Plasma total tryptophan could be rapidly decreased and free tryptophan increased by briefly disturbing food deprived rats. When free tryptophan concentration rose markedly there was an associated increase of brain tryptophan and 5HT turnover. Studies of shock provoked analgesia in rats and cortical evoked potentials in man both suggest that physiological variations of serotonergic activity are sufficient to influence these measures. This raises the possibility that moderate changes of tryptophan supply to the brain could, in some circumstances, alter serotonergic activity.