ABSTRACT
Objective:To investigate the effects of Ginkgo diterpene lactone on depression-like behaviors in a rat model of chronic unpredictable mild stress (CUMS) and its mechanism.Methods:Forty SD rats were randomly divided into five groups, which were control group, CUMS group, CUMS+ low-dose Ginkgo diterpene lactone group (1.5 mg·kg -1·d -1), CUMS+ medium-dose Ginkgo diterpene lactone group (3 mg·kg -1·d -1) and CUMS+ high-dose Ginkgo diterpene lactone group (6 mg·kg -1·d -1). CUMS rat model was established by continuous stress for six weeks, and the rats were given corresponding treatment in the last three weeks. Sucrose preference test was performed during the stress and drug administration, and behavior tests were performed after the stress and drug administration. After behavior tests, hippocampus, hypothalamus and serum samples were collected to detect inflammatory factors and neurotransmitter. Results:Chronic stress caused depression-like behaviors in rats, while continuous treatment with Ginkgo diterpene lactone could effectively improve sucrose preference, forced swimming immobility time and open field test scores in CUMS rats. It was found that Ginkgo diterpene lactone could significantly improve the decreased secretion of IL-1β and IFN-γ in plasma, and significantly increase the secretion of IL-10 and IL-4 caused by CUMS. In addition, CUMS caused hyperfunction of the hypothalamic-pituitary-adrenal (HPA) axis in rats, which manifested as increased secretion of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortisol (COR). The negative feedback of HPA hypermodulated the release of neurotransmitters in the hippocampus, causing the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE) in the brain of CUMS rats to decrease. However, Ginkgo diterpene lactone could significantly inhibit HPA axis hyperfunction and increase neurotransmitter levels in the brain.Conclusions:Ginkgo diterpene lactone can effectively improve the depression-like behaviors of CUMS rats through regulating the immune environment, inhibiting the HPA axis hyperfunction and increasing neurotransmitter release.