Stress Induced Hormone and Neuromodulator Changes in Menopausal Depressive Rats

Abstract

Objective: Previously, we showed that neuromodulators are important factors involved in depression, here we aim to further investigate the interactions between neuromodulators and sex hormone involved in menopause related depression in rats. Methods: Menopausal depression was made with bilateral ovariectomies in female SD rats followed by chronic mild unpredictable stress treatment for 21 days. Thirty six rats were randomly divided into four groups: sham surgery group, sham/stress group, surgery group, surgery/stress group. Then open-field locomotor scores and sucrose intake were employed to observe behavior changes. The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT) in the cerebral spinal fluid and serum adrenocorticotropic hormone (ACTH), cortisone were determined with High-performance liquid chromatography (HPLC). Serum estradiol (E2), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured with radioimmunoassay. Results: The open-field locomotor scores and sucrose intake were significantly decreased after the surgery and stress treatment (p < 0.01). The Serum E₂ level decreased significantly after the surgery (p < 0.01), but serum LH, FSH levels increased significantly in the surgery group than the sham surgery group (p < 0.01). The cortisone levels increased significantly in sham/stress group than that in the sham surgery group during the first 2 weeks at stressful treatment, but decrease afterwards. The monoamine levels in the surgery/stress group were much lower than those in the sham surgery group (p < 0.01). The correlation analysis found that LH and FSH are related more to the neurotransmitter release than E₂. Conclusion: Ovary removal rats showed depression-like behaviors, with LH and FSH increase and monoamine decrease, and the levels of these monoamines in the stress treated groups changed only after the stressful treatment. The LH, FSH hormone increasing might be the reason for the lower monoamine release, which in turn might be the reason for depressed syndromes in the menopause. The cortisone and ACTH in the serum in the surgery/stress group were much higher than that in the sham surgery group.

Keywords: ACTH; FSH; LH; cortisone; depression; menopausal; monoamine.

Figure 1

Open box movement changes after surgery and stress treatment. (A) Both the stress and surgery decreased the horizontal movement. (B) Both the stress and surgery decreased the vertical movement (^*p < 0.01, ^**p < 0.001, repeat measure one-way ANOVA comparisons between the four groups on the 7th days).

Figure 2

Sucrose intake in rats with menopausal depression (^*p < 0.01, ^**p < 0.001, repeated measure one-way ANOVA comparisons between the four groups on the 7th days).

Figure 3

Neuromodulator changes in rats with menopausal depression. (A) Norepinephrine (NE) changes did not change much among the groups (P > 0.05, One-way ANOVA). (B) Dopamine (DA) decreased significantly after the stress and surgery treatment. (C) 5-HT decreased significantly after the stress and surgery treatment. (D) Cortisone increased significantly in the stress treatment groups (^*p < 0.01, ^**p < 0.001, repeat measure one-way ANOVA comparisons between the four groups on the 7th days).

Figure 4

The sex hormone changes after bilateral ovariectomies. (A) Estradiol changes among the groups. (B) Luteinizing hormone (LH) changes among the groups. (C) Follicle-stimulating hormone (FSH) changes among the groups. (D) ACTH changes among the groups. (^*p < 0.01, ^**p < 0.001, repeated measure one-way ANOVA comparisons between the four groups on the 7th days).