Little is known about the psychobehavioral consequences of a dietary deficiency of the amino acid, L-lysine. This report demonstrates that a 4-d long L-lysine deficiency in rats interfered with the normal circadian release of the neurotransmitter serotonin, but not dopamine, measured by in vivo microdialysis in the central nucleus of the amygdala. L-Lysine deficiency was induced by feeding rats a L-lysine-deficient diet. Controls were pair-fed a L-lysine-sufficient diet. Footshock stress-induced anxiety, measured in an elevated plus-maze paradigm, and wrap-restraint stress-stimulated fecal excretion were significantly greater in the L-lysine-deficient rats than in the controls. We conclude that a severe deficiency of dietary L-lysine enhances serotonin release in the amygdala, with subsequent changes in psychobehavioral responses to stress.

S tress and stress-induced anxiety play a major role in functional intestinal disorders (1). The stimulation of intestinal contraction and colonic transit are the most consistent patterns in the motility response of the intestinal tract to acute stress (2, 3); however, the stress-gut interactions are enormously complex (1). Both stress-induced anxiety and intestinal disorders are traced, from among other molecular pathologies, to the inappropriate responses of the central and͞or peripheral serotonin (5-HT) system (4, 5). Among the 5-HT receptors, the 5-HT 4 receptor plays a ''prostress'' role in the gut and throughout the body by mobilizing energy and facilitating behavioral, gastrointestinal, and cardiovascular stress responses (6, 7).5-HT 4 receptors are located within the cells and neurons of the gastrointestinal tract (6,8). Agonists on the 5-HT 4 receptor increase cholinergic transmission (9) and thus contract the smooth muscle in the rat and guinea pig ileum † and the human colon (11). Antagonists on the 5-HT 4 receptor do not affect normal, healthy gut function (12) but prevent the disturbances caused by stress (4) or high 5-HT activity (13). Thus, 5-HT 4 receptor antagonists are promising targets for the treatment of diarrhea-predominant irritable bowel syndrome (12). In addition to their effect on the gastrointestinal tract, 5-HT 4 antagonists block corticosteroid secretion in the adrenal cortex (14), 5-HTinduced tachycardia (15, 16), and stress-induced anxiety (17).However, the 5-HT receptor system is heterogeneous (18), and direct receptor targeting often causes side effects, such as diarrhea, gastric bleeding, and anxiety (19). Therefore, it is not surprising that few satisfying pharmacological treatments of stress-triggered, 5-HT-mediated intestinal disorders exist and that other therapeutic approaches, namely nutritional ones, are sought (20)(21)(22)). An interesting candidate to include in ''nutritional management'' of stress-related gastrointestinal disorders would be an essential amino acid, L-lysine (Lys). Lys blunted stress-induced anxiety in rats (23), whereas a dietary deficiency of Lys increased stress-induced colonic transit and anxiety, because of an enhanced transmission of 5-HT in the amygdala (24).Because the effects of Lys overlap with the ''antistress'' effects of the 5-HT 4 receptor antagonists (4), we hypothesized that dietary Lys could act as a partial antagonist on the 5-HT 4 receptors. The present study examined whether the provision of oral L-lysine might result in the blockage of 5-HT-mediated pathologies linked to stress exposure and͞or 5-HT sensitization in rats. Ileum contractions, stress-induced fecal excretion, diarrhea, anxiety, and tachycardia were monitored. The fractions obtained were washed once by centrifugation with 10-fold volume of the buffer, and the microsomal fraction was stored as receptor at Ϫ80°C until use. To determine the binding degree, the inhibition rate of Lys and a positive reference substance were calculated from binding of a tracer to a receptor. D...

Lysine is a limiting amino acid in diets based on wheat as the staple. In experimental animals, prolonged dietary lysine inadequacy increases stress-induced anxiety. If observed in humans, such a result would have a strong implication for the relationship between nutrition and communal quality of life and mental health. As part of a 3-month randomized double-blind study, we tested whether lysine fortification of wheat reduces anxiety and stress response in family members in poor Syrian communities consuming wheat as a staple food. In the lysine-fortified group, the plasma cortisol response to the blood drawing as a cause of stress was reduced in females, as was sympathetic arousal in males as measured by skin conductance. Lysine fortification also significantly reduced chronic anxiety as measured by the trait anxiety inventory in males. These results suggest that some stress responses in economically weak populations consuming cereal-based diets can be improved with lysine fortification.