Effects of tryptophan depletion on responses to yohimbine in healthy human subjects

Andrew W. Goddard, Dennis S. Charney, Mark Germine, Scott W. Woods, George R. Heninger, John H. Krystal, Wayne K. Goodman, Lawrence H. Price

Research output: Contribution to journalArticle

40 Scopus citations


There is considerable evidence that both the norepinephrine (NE) and serotonin (5-HT) systems are involved in the regulation of human anxiety and fear responses. To assess the modulating effects of central 5-HT levels on NE function, 11 healthy human subjects were studied with placebo-controlled challenge tests involving tryptophan depletion followed by administration of the α-2-adrenergic antagonist yohimbine 0.4 mg/kg IV. Five of the 11 subjects reported a marked increase in feelings of nervousness (≥ 25 mm on a 100 mm analog scale) following the combination test, while 1/11 had this response to yohimbine alone. No subjects had an increase in nervousness during other control tests. The increase in nervousness after the tryptophan depletion-yohimbine test was statistically significant for the whole group, but there were no other unique changes in behavioral, physiologic or biochemical (MHPG, cortisol) variables with this test. These data are discussed in terms of possible functional interactions between the 5-HT and NE neurotransmitter systems.

Original languageEnglish (US)
Pages (from-to)74-85
Number of pages12
JournalBiological psychiatry
Issue number2
StatePublished - Jul 15 1995



  • Anxiety
  • MHPG
  • cortisol
  • norepinephrine
  • serotonin
  • tryptophan

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Goddard, A. W., Charney, D. S., Germine, M., Woods, S. W., Heninger, G. R., Krystal, J. H., Goodman, W. K., & Price, L. H. (1995). Effects of tryptophan depletion on responses to yohimbine in healthy human subjects. Biological psychiatry, 38(2), 74-85. https://doi.org/10.1016/0006-3223(94)00223-P