OBJECTIVE  To establish co-morbidity mouse models of depression and Alzheimer’s disease(AD).

METHODS  Kunming mice were randomly divided into normal group(Control), depression-negative control group(DepNG), depression group(Dep), AD-negative control group(ADNG), AD group, depression-Alzheimer’s disease model group(Dep-AD), and Alzheimer’s disease-depression model group(AD-Dep) according to the degree of sucrose preference. The control group was administered with water freely, DepNG and Dep groups were individual exposed to chronic unpredictable stress(CUS) for 4 or 6 weeks. Meanwhile, the ADNG group and the AD group were administered subcutaneously with D-galactose(D-gal) and intragastric aluminum chloride(AlCl₃) for 7 and 10 weeks, respectively. CUS stress for 6 weeks + D-gal and AlCl₃ administration for 7 weeks in the Dep-AD group, and 10 weeks of D-gal and AlCl₃ administration + 4 weeks of CUS stress in the AD-Dep group. Sucrose preference test and open-field test were used to assess depressive-like behaviour in mice, and Morris water maze test was used to detect learning memory ability.

RESULTS  Compared with the control group, the DepNG group showed no significant differences in the related indicators, whereas the Dep and Dep-AD groups exhibited significant reductions in sucrose preference, horizontal and vertical activity frequencies. The escape latency was increased and staying target quadrant time was decreased significantly in the Dep-AD group, which were comparable to the AD group. Compared with the control group, the ADNG group showed no significant differences, while the AD and AD-Dep groups exhibited a significant increase in escape latency and significant decreases in the time spent in the target quadrant and the number of platform crossings. The AD-Dep group showed significantly reduced sucrose preference, horizontal and vertical activity frequencies, to a level comparable with the Dep group.

CONCLUSION  Both Dep-AD model of mice and AD-Dep model of mice can be successfully established.