EFFECT OF ACUTE TRYPTOPHAN DEPLETION ON BEHAVIORAL, CARDIOVASCULAR, AND HORMONAL SENSITIVITY TO CHOLECYSTOKININ-TETRAPEPTIDE CHALLENGE IN HEALTHY-VOLUNTEERS

Recent data suggest that serotonergic (5-HT) mechanisms may mediate th e anxiogenic effects of cholecystokinin (CCK)-related peptides. Accord ingly, we investigated the effect of lowering plasma tryptophan to the elicitation of behavioral, cardiovascular, and hormonal changes in he althy volunteers challenged with the tetrapeptide CCK agonist, CCK-4. Forty men without personal or family history of psychiatric disorders were randomly assigned to either a tryptophan-free amino acid mixture, which decreases central 5-HT concentrations, or a control mixture. Fi ve hours after administration of the amino acid mixture, all subjects received a single intravenous injection of CCK-4. The main finding of the study was that acute depletion of tryptophan failed to modify the panicogenic and cardiovascular effects of CCK-4 although it did enhanc e CCK-4-mediated increases in ACTH/cortisol and prolactin secretion. W hile these findings suggest that at least part of the neuroendocrine a ction of CCK-4 is mediated through the 5-HT system, the locus of the 5 -HT-CCK interaction and the specific 5-HT receptor subtype involved re mains to be determined.