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 the anxiogenic effects of cholecystokinin (CCK)-related peptides. Accordingly, we investigated the effect of lowering plasma tryptophan to the elicitation of behavioral, cardiovascular, and hormonal changes in healthy 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. Five 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 enhance CCK-4-mediated increases in ACTH/cortisol and prolactin secretion. While these findings suggest that at least part of the neuroendocrine action 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 remains to be determined.
Koszycki
D
D
Psychobiology and Clinical Trials Research Unit in Anxiety, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Zacharko
R M
RM
Le Melledo
J M
JM
Young
S N
SN
Bradwejn
J
J
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D008297:Male; D010200:Panic / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology; D013758:Tetragastrin / Q000494:pharmacology*
D013758:Tetragastrin; D012701:Serotonin