Abstract： Objective To explore the changes of monoamine neurotransmitters in serum,hippocampus and medulla oblongata of experimental depression rats under simulated space-specific environment. Methods Thirty rats with similar behavior scores at open field test were randomized into model group and control group (n=15 each). Classical pattern of depression combined with simulated spacespecific environment was used to establish the rat models of depression in the model group, whereas the rats in the control group received no treatment. Under simulated space-specific environment, the changes of behavior were observed and the changes of neurotransmitters including 5 - hydroxytryptamine (5 - HT) ,dopamine (DA) and norepinephrine (NE) in serum, hippocampus and medulla oblongata were measured.Results Compared with controls, the depressed rats walked through fewer squares, experienced less upright actions, more grooming and time at the central square (all P＜ 0.05). In the model rats, the serum contents of 5-HT [ (334.23±110.45)μg/L vs (248.76±51.83)μg/L], DA [ (109.19±26.86) μg/L vs (88.42±12.63) μg/L] and NE [ ( 102.46±39.31 ) μg/L vs (74.88±12.04) ] were significantly elevated (all P＜0.05),and NE [ (9.99±8.02) μg/L vs (25.41±5.68)μg/L,P＜0.05] in hippocampus was reduced, as compared with controls. Conclusion The major cause of space environment-related depression may be associated with the reduced level of NE in hippocampus and not associated with the reduced levels of 5-HT and DA in serum.