Control of Brain Monoamine Synthesis by Diet and Plasma Amino Acids

The rates at which monoaminergic neurons in rat brains synthesize their neurotransmitters depend on the availability of the amino acid precursors tryptophan (for serotonin) and tyrosine (for dopamine and norepinephrine). The administration of tryptophan, the injection of insulin, or the consumption of a single protein-free high-carbohydrate meal all elevate brain tryptophan levels and, soon thereafter, the levels of serotonin and its major metabolite 5-hydroxyindole acetic acid. The addition of protein to the meal suppresses the increases in brain tryptophan and serotonin, because protein contributes to plasma considerably larger amounts of the other neutral amino acids (e.g., leucine, phenylalanine) than of tryptophan, and these other amino acids compete with tryptophan for uptake into the brain. The elevation of brain tyrosine (by injection of the amino acid or consumption of a single 40% protein meal) accelerates brain catecholamine synthesis, as estimated by measuring brain dopa accumulation after decarboxylase inhibition, or brain catecholamine accumulation after inhibition of monoamine oxidase. These observations suggest that serotonin- and catecholamine-containing brain neurons are normally under specific dietary control.