Abstract: Objective To explore changes of the concentration of 5-hydroxytryptamine (5-HT) in hippocampus and the expression of tryptophan hydroxylase 2(TPH2) in median raphe nuclei in the perimenopausal depression model rats. Methods The animal model was established by resecting the ovaries of female rats, then giving isolation-housing in combination with chronic unexpected mild stress(CUMS) for 21 days. Behavioral tests were used to evaluate the model. High performance liquid chromatogram-electrochemical detection was employed to measure 5-hydroxytryptamine (5-HT) in hippocampus. Reverse transcription- polymerase chain reaction(RT-PCR) and immunohistochemistry were to detect the relative expression of TPH2 mRNA and TPH2 immunoreactive neurons in median raphe nuclei. Results After 21 days of CUMS, both crossing and rearing in model group were reduced in Open-field test，and percentage of sugar consumption was too. The concentration of 5-HT in hippocampus was lowered in the model one, the relative expression of TPH2 mRNA and the number of TPH2 immunoreactive neurons in raphe nuclei were too. Conclusion Perimenopausal depression model could successfully be induced by ovariectomy, isolation -housing in combination with 21 days of CUMS. The decrease of 5-HT in hippocampus might be through reducing the expression of TPH2 in median raphe nuclei, which leads to lower the synthesis of 5-HT.

Key words: chronic unexpected mild stress, 5-hydroxytryptamine, tryptophan hydroxylase 2