Standardization of formulations for the acute amino acid depletion and loading tests

J Psychopharmacol. 2015 Apr;29(4):363-71. doi: 10.1177/0269881114565141. Epub 2015 Jan 13.


The acute tryptophan depletion and loading and the acute tyrosine plus phenylalanine depletion tests are powerful tools for studying the roles of cerebral monoamines in behaviour and symptoms related to various disorders. The tests use either amino acid mixtures or proteins. Current amino acid mixtures lack specificity in humans, but not in rodents, because of the faster disposal of branched-chain amino acids (BCAAs) by the latter. The high content of BCAA (30-60%) is responsible for the poor specificity in humans and we recommend, in a 50g dose, a control formulation with a lowered BCAA content (18%) as a common control for the above tests. With protein-based formulations, α-lactalbumin is specific for acute tryptophan loading, whereas gelatine is only partially effective for acute tryptophan depletion. We recommend the use of the whey protein fraction glycomacropeptide as an alternative protein. Its BCAA content is ideal for specificity and the absence of tryptophan, tyrosine and phenylalanine render it suitable as a template for seven formulations (separate and combined depletion or loading and a truly balanced control). We invite the research community to participate in standardization of the depletion and loading methodologies by using our recommended amino acid formulation and developing those based on glycomacropeptide.

Keywords: Acute tryptophan depletion and loading; acute tyrosine and phenylalanine depletion; anxiety; behaviour; branched-chain amino acids; glutamatergic function; glycomacropeptide; serotonin; tryptophan; tyrosine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Branched-Chain / administration & dosage*
  • Animals
  • Humans
  • Phenylalanine / blood*
  • Rodentia
  • Species Specificity
  • Tryptophan / blood*
  • Tyrosine / blood*


  • Amino Acids, Branched-Chain
  • Tyrosine
  • Phenylalanine
  • Tryptophan