Acute antidepressant-like and antianxiety-like effects of tryptophan in mice.
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.
Wong
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PT
Department of Pharmacology, Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore 119260. phcwth@nus.edu.sg
Ong
Y P
YP
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology*; D000928:Antidepressive Agents / Q000378:metabolism / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D012702:Serotonin Antagonists / Q000494:pharmacology; D014364:Tryptophan / Q000378:metabolism / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D014364:Tryptophan; D008550:Melatonin; D010134:Fenclonine