The aim of this study was to determine the effect of pharmacological doses of melatonin (MEL) and L-tryptophan (L-TRP) on depression-like behavior in female rats submitted to the forced swimming test (FST) after 2, 4, 6 or 8 weeks of treatment. This will allow exploring the different mechanisms of L-TRP actions particularly that due to its conversion into MEL. For this purpose, four groups of 24 rats each were constituted; (Group 1: Control): received saline solution NaCl (0.9%), (Group 2:

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... : received 4 mg/Kg of MEL, (Group 3: L-TRP4): received 4 mg/Kg of L-TRP and (Group 4: L-TRP20): received 20 mg/Kg of L-TRP. Animals of each group were distributed on 4 subgroups of 6 rats submitted to different time treatments. The duration of immobility (TIM) and struggling period (TST) of rats in FST were measured after 2, 4, 6 and 8 weeks of drug treatment and the effects of MEL and L-TRP were compared. Chronical administration of different doses of MEL or L-TRP failed to induce any anti-depressant activity in rats subjected to FST after 2 weeks of treatment. However, after 4 weeks, daily administration of MEL at 4 mg/Kg significantly reduced the immobility period and enhanced struggling time. After 6 weeks, MEL at 4 mg/Kg and L-TRP at 20 mg/Kg were both effective in reducing immobility and increasing struggling movement, their effects being statistically comparable. All treatments were able to significantly reduce immobility time and increase struggling duration after 8 weeks, but L-TRP at 4 mg/Kg was less potent than MEL and L-TRP at 20 g/Kg. The antidepressant-like activity of L-TRP was dose and time dependent, and that of MEL was time dependent. In conclusion, the study showed that at pharmacological doses, MEL and L-TRP have anti-depressant action, and such effect is dependent on time treatment; MEL is more effective than L-TRP. In conclusion, L-TRP, through MEL, 5-HT or by itself could modulate aminergic neurotransmission in the different brain areas to ensure its behavioral effects.