Background and Aim: Depression is a serious mental disorder. Despite the availability of numerous medications, there are still constraints, such as high cost and adverse effects in the pharmacological treatment of depression. The Identification of bioactive plant compounds is of interest as an alternative treatment. Citral is one of the monoterpenes found in lemon peel oil with numerous therapeutic effects. This study investigated the effects of Citral on depression-like behaviors in mice under chronic unpredictable mild stress (CUMS).

Methods: 48 male mice were randomly divided into 6 groups of 8: control, CUMS, vehicle + CUMS, fluoxetine 20 mg/kg + CUMS, Citral 100 mg/kg + CUMS, and Citral 200 mg/kg + CUMS. Except for the control group, mice were exposed to stressors according to a schedule for 6 weeks. In the last two weeks, treatments were administered orally. Then, depression-like behaviors were evaluated with sucrose preference, open field, forced swimming, and tail suspension tests.

Results: Compared to vehicle, Citral decreased the sucrose preference in CUMS-mice (p < 0.001). Citral 200mg/kg increased the locomotor activities in the center zone (p < 0.05), and citral 100 and 200 mg/kg decreased the locomotor activities in the peripheral zone of an open field (p < 0.001). In the tail suspension test citral 100 and 200 mg/kg respectively with significant levels p < 0.05 and p < 0.01, the forced swimming test with significant levels p < 0.01 and p < 0.001 reduced the immobility time.

Conclusion: Citral, like the standard drug, fluoxetine, could exert significant antidepressant effects in depressed and CUMS-mice.‎