Objective: Previous studies have demonstrated that fingered citron volatile produced antidepressant-like action in various mouse models with behavioral despair. The present study aimed to examine whether fingered citron volatile could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. Method: Ninety male Wistar rats were randomly divided into six groups as follows: control

model

positive control (orally given fluoxetine 10 mg·kg-1 for 21 days)

low

middle and high dosages of fingered citron volatile (orally given 150

300

600 mg·kg-1 of fingered citron volatile for 21 days). All groups except control were exposed to chronic stress for 21 days to establish depression model and every rat was given corresponding drugs simultaneously. After 21 days

the behavior changes were measured by sucrose preference and open-field

serum corticosterone level was measured by radio-immunity and brain-derived neurotrophic factor (BDNF) protein levels was measured by Western-blot. Result: CUMS being lasted for 3 weeks

caused depression-like behavior in rats

as indicated by the significant decrease in sucrose preference (from 88.1%±13.3% to 60.5%±9.8%) and in open-field scores (from 123.5±21.3 to 38.2±5.9 and from 72.5±12.7 to 17.1±5.1

respectively).Whereas serum corticosterone level was significantly increased in rats exposed to CUMS·L-1 to (117.6±19.3) μg·L-1]

and BDNF protein expression were decreased (from 0.22±0.04 to 0.07±0.02) in CUMS-treated rats. Daily intragastric administration of fingered citron volatile (150

300

600 mg·kg-1) during the three weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. As the sucrose preferences in 300

600 mg·kg-1 fingered citron volatile were 70.7%±10.2% and 77.1%±11.9% (P<0.05 and P<0.01); the horizontal scores in 150

300

600 mg·kg-1 fingered citron volatile were 87.7±15.4

98.3±19.7 and 110.3±28.9 (P<0.05

P<0.05 and P<0.01); the vertical scores in 300

600 mg·kg-1 fingered citron volatile were 24.5±6.3 and 29.2±7.2 (P<0.05 and P<0.01); the serum corticosterone levels in 300

600 mg·kg-1 fingered citron volatile were (90.1±13.5) μg·L-1 and (77.5±10.7) μg·L-1(P<0.05 and P<0.01);the BDNF levels in 300

600 mg·kg-1 fingered citron volatile were 0.15±0.03 and 0.18±0.03 (P<0.05 and P<0.01). Conclusion: The results suggest that the antidepressant-like actions of fingered citron volatile may be mediated by modulating the CORT concentration and increasing the expression of BDNF in hippocampus tissues.