Acute antidepressant-like and antianxiety-like effects of tryptophan in mice

Pharmacology. 2001;62(3):151-6. doi: 10.1159/000056088.


The antidepressant-like, antianxiety-like and sedative effects of tryptophan (TRP), in the absence and presence of p-chlorophenylalanine (p-CPA), and melatonin were studied in mice using the forced-swimming test, open-field test and activity cage, respectively. Single-dose TRP caused an antidepressant-like effect dose dependently up to 125 mg/kg. No significant effect was observed, however, when the TRP dose was increased to 250 mg/kg, i.e. a reversal of effect occurred at high dose. With p-CPA pretreatment, the effects observed at 125 and 250 mg/kg TRP were similar to those obtained at 50 and 125 mg/kg without p-CPA pretreatment, respectively. Melatonin also caused an antidepressant-like effect in a similar manner, but appeared to be less potent than TRP. These results strongly indicate that the antidepressant-like effect of TRP was due to its conversion to 5-hydroxytryptamine (5-HT). An antianxiety-like effect was observed for TRP only at 250 mg/kg dose together with p-CPA pretreatment, while no sedative effect was observed at all. In contrast, melatonin did not produce any antianxiety-like effect, but produced sedation at 200 mg/kg dose. It may be concluded that the antianxiety-like effect of TRP is unrelated to 5-HT and melatonin formation, but associated with TRP itself or, perhaps, with other anxiolytic metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents / metabolism
  • Anti-Anxiety Agents / pharmacology*
  • Antidepressive Agents / metabolism
  • Antidepressive Agents / pharmacology*
  • Anxiety / drug therapy
  • Behavior, Animal / drug effects
  • Depression / drug therapy
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Fenclonine / pharmacology*
  • Male
  • Melatonin / metabolism
  • Melatonin / pharmacology*
  • Mice
  • Serotonin Antagonists / pharmacology
  • Tryptophan / metabolism
  • Tryptophan / pharmacology*


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Enzyme Inhibitors
  • Serotonin Antagonists
  • Tryptophan
  • Melatonin
  • Fenclonine