【Animal modeling】-Construction and evaluation of a rat model of depression and insomnia

  Objective To use the method of chronic unpredictable moderate stress combined with rapid and chronic modified multi-platform water environment sleep deprivation to replicate the depression and insomnia rat model, compare the two modeling methods, and choose the best modeling method.

  Methods 84 rats were randomly divided into blank group, environmental control group, chronic stress group, 72 h sleep deprivation group, chronic stress + 72 h sleep deprivation group, 21 d sleep deprivation group, and chronic stress + 21 d according to body weight. Sleep deprivation group, a total of 7 groups, 12 in each group. After 14 days of stress modeling and compound modeling, behavioral tests were performed to test the depression and insomnia-like behavior of rats, and ELISA was used to detect corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone in serum of rats. (CORT) content and glutamate (Glu), γ-aminobutyric acid (GABA) content in hypothalamus, NE, 5-HT and DA content in rat hypothalamus were determined by HPLC-ECD. HE staining was used to observe the pathological changes of the hypothalamus of the rats in each group.

  Results Compared with the blank group, the rats in the CUMS + 72 h SD group and the CUMS + 21 d SD group showed a significant decrease in body weight growth rate and food intake, significantly decreased the number of autonomous activities in the open field test, and increased the number of fecal pellets. In the CUMS + 21 d SD group, the serum CRH, ACTH and CORT contents also increased significantly, and the lower and lower levels were significantly increased. The content of Glu in the thalamus was significantly increased, the content of GABA was significantly decreased, and the content of monoamine transmitters was decreased. The arrangement of neurons in the hypothalamus was disordered, the gap became larger, and the vacuolar-like characteristics were significant.

  Conclusion The method of chronic unpredictable moderate stress combined with 18 hours a day for 21 days of sleep deprivation in a modified multi-platform water environment can stably replicate the depression and insomnia rat model.