Relationships between tryptophan, diet, 5-hydroxytryptamine metabolism, 5-hydroxytryptamine function and behavior

The role of tryptophan availability in the regulation of 5-hydroxytryptamine (5HT) metabolism and function has been examined in rats and humans, by manipulation of dietary components. It was demonstrated that in the rat, protein and carbohydrate can alter 5HT levels in peripheral tissues as well as brain. A new method for the determination of 5HT in the cisternal cerebrospinal fluid (CSF) of the rat was developed and used as an index of functional 5HT, using pharmacological agents known to act on 5HT function. Using this technique, it was then shown that tryptophan administration potentiates the release of 5HT when the animals are aroused, and thus when their 5HT neurons are firing at high rates. However, the smaller changes in brain 5HT after ingestion of protein or carbohydrate did not lead to altered CSF 5HT. In humans, similar conclusions were drawn. The administration of an amino acid mixture deficient in tryptophan significantly altered macronutrient selection, a behavior thought to be mediated by lowered tryptophan availability and 5HT function. However, when protein or carbohydrate breakfasts were given, no effect on macronutrient selection was observed, suggesting that the physiological changes resulting from dietary intake were not affecting functional 5HT. The final study measured amine precursors and metabolites in human lumbar CSF after the administration of protein or carbohydrate breakfasts and supported this hypothesis. No effects on CSF tryptophan or 5-hydroxyindoleacetic acid, the major metabolite of 5HT, were observed. In conclusion, the results of these studies suggest that, though large changes in precursor availability can alter 5HT function, the effects of dietary intake on 5HT metabolism are not normally of sufficient magnitude to alter 5HT function in rats or humans, or brain 5HT metabolism in humans