Tryptophan depletion during continuous CSF sampling in healthy human subjects

被引:0
作者
Carpenter L.L. [1 ]
Anderson G.M. [2 ]
Pelton G.H. [3 ]
Gudin J.A. [4 ]
Kirwin P.D.S. [3 ]
Price L.H. [1 ]
Heninger G.R. [3 ]
McDougle C.J. [5 ]
机构
[1] Butler Hospital, Lab. Clin. Neurosci., Dept. P., Providence, RI
[2] Yale Child Study Center, Yale University School of Medicine, New Haven, CT
[3] Clinical Neuroscience Research Unit, Connecticut Mental Hlth. Ctr., D., New Haven, CT
[4] Department of Anesthesia, Yale University School of Medicine, New Haven, CT
[5] Child and Adolescent Psychiatry, Indiana Univ. School of Medicine, Indianapolis, IN
关键词
5-HIAA; Amino acids; CSF; Serotonin; Tryptophan;
D O I
10.1016/S0893-133X(97)00198-X
中图分类号
学科分类号
摘要
The tryptophan (TRP) depletion paradigm has been employed to investigate mood and behavioral effects of acutely lowering plasma TRP, and presumably brain serotonin (5-hydroxytryptamine [5-HT]) levels through administration of a special diet and/or amino acid drink. Our goal was to test the assumption that a corresponding fall in central levels of TRP and 5-HT (measured by its major metabolite, 5-hydroxyindoleacetic acid [5-HIAA]) occurs during the standard execution of this method in healthy adult subjects. Three males and two females completed the protocol, which included a one-day low-TRP diet and a TRP-free amino acid drink. Lumbar puncture was performed, with placement of an indwelling catheter connected to a peristaltic pump and fraction collector. Cerebrospinal fluid (CSF) was sampled continuously for a 13.5- hour period (before, during, and after the drink) with fractions removed every 15 minutes. Plasma samples were simultaneously obtained. CSF TRP levels and plasma TRP levels were highly correlated, falling a mean of 92% and 85% from baseline, respectively. CSF nadirs were reached several hours after plasma nadirs. CSF 5-HIAA decreased modestly (24% to 40%, mean 31% change from baseline), with lowest concentrations observed 8-12 hours after the amino acid drink. These data suggest that TRP depletion results in substantial declines in central 5-HT turnover.
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页码:26 / 35
页数:9
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