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BACKGROUND: Ideal model of poststroke depression (PSD) may be induced in rats guided by the theoretical evidence that primary endogenous mechanism and reactivity mechanism theories for PSD in human being.OBJECTIVE: To investigate the feasibility of comprehensive methods to induce PSD models in rats.DESrGN: A randomized controlled animal trial.SETTING: Department of Neurology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine.MATERrALS: Male SD rats of SPF degree, weighing 350-500 g, were provided by the experimental animal center of Chengdu University of Traditional Chinese Medicine. The rats were raised for 1 week adaptively, then screened behaviorally by open-field test and passive avoidance test. Forty-five rats with close scores were randomly divided into normal control group (n =10), simple stroke group (n =10), stress group (n =10) and PSD group (n =15).METHODS: The experiments were carried out in the laboratory of Chengdu University of Traditional Chinese Medicine from July 2002 to February 2003. ① Rat models of focal cerebral ischemia were induced by thread embolization, then treated with separate raising and unpredictable stress to induce PSD models. ②The neurologic deficit was evaluated by Longa 5-grade standard (the higher the score, the severer the neurologic deficit) and horizontal round rod test (normal rat could stay on it for at least 3 minutes). ③ The behavioral changes of PSD rats were evaluated by the saccharin water test, open-field text and passive avoidance test,including the changes of interest, spontaneous and exploratory activities, etc. ④ The levels of monoamine neurotransmitters, including norepinephrine (NE), serotonin (5-HT) and dopamine, in brain were determined using fluorospectrophotometry.MAIN OUTCOME MEASURES: ① Score of Longa 5-grade standard; Stayed time in the horizontal round rod test;② Amount of saccharin water consumption; Open-field text: time stayed in the central square, times wondering among squares, times for upright grooming; Passive avoidance test: total number of shocks, duration of being shocked; ③ Contents of NE, 5-HT and dopamine in brain.RESULTS: Six rats died and 3 rats failed in the model establishment, and finally 36 rats were involved in the analysis of results. ① 22 stroke rats were evaluated by the Longa 5-grade standard (including 9 in the stroke group and 13 in the PSD group), the scores at 4, 8 and 24 hours after consciousness were 2.58±0.69, 2.32±0.58 and 1.37±0.60, respectively. ② 20 stroke rats were evaluated by the horizontal round rod test (including 8 in the stroke group and 12 in the PSD group), and the time stayed on the rod at 1, 3 and 5 days after stroke were (110.94±31.40), (149.53±16.56) and (169.88±8.44) s, respectively. ③ The body masses at 7 and 14 days after stroke were significantly lower in the PSD group than the normal control group [(348.8±47.7), (390.9±22.9) g,P＜ 0.05; (321.7±43.8), (392.6±23.5) g, P＜ 0.01]. ④ The amount of saccharin-water consumption was significantly lower in the PSD group than the normal control group [(8.48±1.15), (113.0±11.8) mL/kg, P ＜ 0.01].⑤The PSD rats had reduced activities in the open-field test and passive avoidance deficits, which were obviously different from those in the normal control group (P＜ 0.05). ⑥ The NE and 5-HT contents in bilateral frontoparietal cortexes and brain stem in the PSD group were significantly decreased as compared with those in the normal control group (P ＜ 0.05); The contents of dopamine in left frontoparietal cortex and brain stem were also obviously lower than those in the normal control group (P＜ 0.05).CONCLUSION: It is correct and feasible to induce PSD rat model by giving separating raising and stress to rat models of focal cerebral ischemia established by thread embolization of intal carotid artery.