We have observed over the past several years that the availability of tryptophan (trp) and tyrosine (tyr) to the brain influences the rates of which these amino acids are converted to serotonin (5HT) and the catecholamines (CAM), respectively. Diet (even the ingestion of single meals) has been shown to modify TRP and TYR uptake into brain, and thus the rates of formation of 5HT and CAM, food ingestion, by altering brain neurotransmitter synthesis and levels, may also modify the amounts of transmitters released when neurons depolarize. If so, then the diet might modify measurable brain outputs, such as particular behaviors and neuroendocrine secretions. However, few studies have fully explored the potential relationships among diet, brain neurotransmitters, and behavior- neuroendocrine function. It is the intent of the proposed research program to determine whether diet-induced modifications in brain neurotransmitter formation lead to overt changes in specific behaviors and hormonal secretions. In particular, the following outputs will be studies: (1) Pain sensitivity: pain sensitivity has been shown in rats to be correlated most clearly with the activity of 5HT neurons in brain. Using the flinch-jump test in rats, we will study the effects of diets, amino acids, and drugs on the behavioral output. (2) sleep: 5HT neurons have also been closely associated with the control of sleep. We will study, in humans, the effects of the administration of tryptophan, tyrosine, or other amino acids, and of the ingestion of particular diets, on a variety of sleep parameters (using sleep EEGs and subject sleep ratings) and on the plasma amino acid pattern. (3) Food intake regulation: 5HT and CAM neurons in brain are known to be involved in the control of nutrient intake. We will use the self-selecting rat (animal is allowed to choose the amount of a particular nutrient he consumes each day, be giving him access to 2 or more foods, differing in their content of the nutrient of interest) to study the ability of the injection of TRP, TYR, or other amino acids or drugs, or the ingestion of particular meals to modify the amounts of protein or carbohydrates the animal elects to consume subsequent to the experimental treatment. (4) Pituitary hormone sections: the secretions of growth hormone (GH) and prolactin (PL) have been shown to be influenced by drugs that modify the amounts of 5HT and CAM receptors in the brain, we will thus study the secretion of GH and PL following the administration of TRP, TYR or other amino acids or drugs, and following the ingestion of particular meals that should alter brain 5HT or CAM synthesis. Finally, although most studies will focus on 5HT and CAM, we also intend to explore the possibility that diet-induced changes in acetylcholine (ACH) formation in brain influence the brain outputs under investigation. The results of this line of study, aside from elucidating potentially-important brain mechanisms, could also aid in the management of certain disease states involving altered levels and release of 5HT, CAM or ACH by brain neurons. By providing simple, dietary treatments for helping to correct the neurotransmitter imbalance.
