Effect of concomitant administration of tryptophan on depression-related and anxiety-like behaviors of fluoxetine treated adult rats

Abstract

Objective To investigate the effects of concomitant administration of tryptophan on depression-related and anxiety-like behaviors of fluoxetine treated adult rats. Methods Sixty male Wistar rats were divided into the following groups by randomized block design: control group, L-tryptophan group, fluoxetine group, and experimental group (n=15); 9 g/L sodium chloride injection (5 mL/kg), 50 mg/kg L-tryptophan, 10 mg/kg fluoxetine and both 50 mg/kg L-tryptophan and 10 mg/kg fluoxetine were, respectively, given to the rats in the above four groups via intragastric administration; depression models were established by 21 d-long-term chronic, medium and unpredictable stress stimulation. The modified forced swimming test (FST) was used to detect the times spent in immobility behavior, swimming behavior and climbing behavior; and elevated plus-maze (EPM) was employed to detect the times spent in open arms, closed arms and center area, and ratio of entries into open arms to the total entries; while tryptophan levels in cerebrospinal fluid were measured by high performance liquid chromatography. Results The times spent in immobility behavior, swimming behavior and climbing behavior showed significant differences among the four groups (P<0.05); both fluoxetine and tryptophan had significant influences in FST results. The times spent in open arms, closed arms and center area showed significant differences among the four groups (P<0.05); fluoxetine had significant influences in EPM results, and tryptophan had no significant influences in times spent in open arms, closed arms and center area; moreover, there was no significant interaction between tryptophan and fluoxetine treatments in parameters of FST and EPM. Significant difference of tryptophan level was noted among the four groups (F=6.874,P=0.002); that in the experimental group was significantly higher than that in the fluoxetine and control group (P<0.05). Conclusions Tryptophan can increase depressive-related behavior, but not alter anxiety-like behavior. Fluoxetine can decrease depression-related behavior, but induce anxiety. Concomitant use of tryptophan and fluoxetine does not alter anxiety-like behavior and the antidepressant effect of fluoxetine is not enhanced. Key words: Tryptophan; Fluoxetine; Depression; Anxiety; Interaction effect