Inhibition of hormonal and behavioral effects of stress by tryptophan in rats

Nutr Neurosci. 2019 Jun;22(6):409-417. doi: 10.1080/1028415X.2017.1395551. Epub 2017 Nov 3.


Objectives: Stress in known to alter hormonal systems. Pharmacological doses of tryptophan, the essential amino acid precursor of serotonin, increase circulating leptin and decrease ghrelin in normal healthy adults. Because systemically injected leptin inhibits stress-induced behavioral deficits and systemically injected serotonin modulates leptin release from the adipocytes, we used tryptophan as a pharmacological tool to modulate hormonal and behavioral responses in unstressed and stressed rats.

Methods: Leptin, ghrelin, serotonin, tryptophan, and behavior were studied in unstressed and stressed rats following oral administration of 0, 100, 200, and 300 mg/kg of tryptophan.

Results: Following oral administration of tryptophan at a dose of 300 mg/kg, circulating levels of serotonin and leptin increased and those of ghrelin decreased in unstressed animals. No effect occurred on 24-hours cumulative food intake and elevated plus maze performance. Exposure to 2 hours immobilization stress decreased 24 hours cumulative food intake and impaired performance in elevated plus maze monitored next day. Serum serotonin decreased, leptin increased, and no effect occurred on ghrelin. Stress effects on serotonin, leptin, food intake, and elevated plus maze performance did not occur in tryptophan-pretreated animals. Tryptophan-induced decreases of ghrelin also did not occur in stressed animals.

Conclusion: The findings show an important role of serum serotonin, leptin, and ghrelin in responses to stress and suggest that the essential amino acid tryptophan can improve therapeutics in stress-induced hormonal and behavioral disorders.

Keywords: Anxiety/depression; Behavior; Ghrelin; Hormones; Leptin; Obesity; Stress; Tryptophan.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Body Weight / drug effects
  • Eating / drug effects
  • Ghrelin / blood*
  • Leptin / blood*
  • Male
  • Rats, Wistar
  • Restraint, Physical
  • Serotonin / blood*
  • Stress, Psychological / blood*
  • Tryptophan / administration & dosage*


  • Ghrelin
  • Leptin
  • Serotonin
  • Tryptophan