BACKGROUND: Restraint stress is a typical psychophysiological stressor. Simulating the early passion and difficulty in walking of patients after attack of stroke meets onset features. OBJECTIVE: To evaluate the effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury, and to investigate the feasibility for its being as modeling method of depression model after stroke. DESIGN: A randomized controlled animal experiment. SETTING: Department of Clinical Medicine, Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA. MATERIALS: Forty-eight male Sprague-Dawley rats, weighing 240–270 g, provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA were used in the current study. METHODS: The experiments were carried out in the Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA between August 2005 and August 2006. ①Experiment intervention: The rats were randomized into middle cerebral artery occlusion-reperfusion (MCAO) +stress group, simple MCAO group, sham-operation + stress group and simple sham-operation group, with 12 rats in each group. Rats in the first two groups were developed into cerebral ischemia/reperfusion models by suture-occluded method. Rats in the MCAO+stress group were modeled and restraint stress scheme was performed. At week 5 after modeling, the rats were placed in self-made restraining tubes, 2 hours/time, once a day, for 2 successive weeks. The common carotid artery, external and internal carotid arteries of rats in the latter two groups were exposed. The stress way of sham-operation+ stress group was the same as that of MCAO+ stress group. ②The neurological status grading and motor performance evaluation (screen test, rota-rod test and balance beam test) were conducted in rats with simple sham-operation group and MCAO group before, 1st and 28th days after modeling. Depression-like behavior test was performed in the rats of each group by sucrose preference test and open field test at the end of the experiment. MAIN OUTCOME MEASURES: Changes of depression-like behaviors of rats in each group. RESULTS: Forty-eight rats were involved in the experiment. Two rats with meningeal irritation sign were excluded from simple MCAO group, and one rat in the MCAO+stress group died of some unclear causes during the experiments. The other 45 rats entered the stage of finial analysis. ① Depression-like behavior assessment results: The rats in the MCAO+ stress group had a significantly decreased preference for sucrose solution, crossing and rearing scores, and increased immobility duration after the 14-day restraint stress, compared with those in other three groups (all P < 0.05). ②The neurological status grading and motor performance evaluation: There were significant differences in the two indexes of rats in the simple MCAO group before, 1st and 28th days after modeling (P < 0.01), while there was no significant difference before and 28th days after modeling (P > 0.05). There were no significant changes in sham-operation group at each time point (P > 0.05). CONCLUSION: After being exerted restraint stress, the rats with transient focal ischemic injury may show obvious depression-like behaviors. Therefore, restraint stress can be used as a novel animal modeling method for further studying biological mechanism in central nervous system of post-stroke depression animals. BACKGROUND: Resting in early depression and difficulty in walking of patients after attack of stroke meets onset features. OBJECTIVE: To evaluate the effect of restraint stress on depression-like behaviors in rats after transient focal cerebral ischemic injury , and to investigate the feasibility for its being as modeling method of depression model after stroke. DESIGN: A randomized controlled animal experiment. SETTING: Department of Clinical Medicine, Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA. MATERIALS: Forty -eight male Sprague-Dawley rats, weighing 240-270 g, provided by the Experimental Animal Center of the Fourth Military Medical University of Chinese PLA were used in the current study. METHODS: The experiments were carried out in the Faculty of Aerospace Medicine of the Fourth Military Medical University of Chinese PLA between August 2005 and August 2006. ①Experiment inte rvention: The rats were randomized into middle cerebral artery occlusion-reperfusion (MCAO) + stress group, simple MCAO group, sham-operation + stress group and simple sham-operation group, with 12 rats in each group. Rats in the first two groups were developed into cerebral ischemia / reperfusion models by suture-occluded method. Rats in the MCAO + stress group were modeled and restraint stress scheme was performed. At week 5 after modeling, the rats were placed in self-made restraining tubes, 2 hours / The common carotid artery, external and internal carotid arteries of rats in the latter two groups were exposed. The stress way of sham-operation + stress group was the same as that of MCAO + stress group. ② The neurological status grading and motor performance evaluation (screen test, rota-rod test and balance beam test) were conducted in rats with simple sham-operation group and MCAO group before, 1st and 28th days after modeling. Depression-like beh aviortest was performed in the rats of each group by sucrose preference test and open field test at the end of the experiment. MAIN OUTCOME MEASURES: Changes of depression-like behaviors of rats in each group. RESULTS: Forty-eight rats were involved in the experiment. Two rats with meningeal irritation sign were excluded from simple MCAO group, and one rat in the MCAO + stress group died of some unclear causes during the experiments. The other 45 rats entered the stage of finial analysis. ① Depression-like behavior assessment results: The rats in the MCAO + stress group had a significantly decreased preference for sucrose solution, crossing and rearing scores, and increased immobility duration after the 14-day restraint stress, compared with those in the other three groups (all P <0.05). ②The neurological status grading and motor performance evaluation: There were significant differences in the two indexes of rats in the simple MCAO group before, 1st and 28th days after modeling (P <0.01), w There were no significant changes in sham-operation group at each time point (P> 0.05). CONCLUSION: After being exerted restraint stress, the rats with transient focal, ischemic injury may show obvious depression-like behaviors. Therefore, restraint stress can be used as a novel animal modeling method for further studying biological mechanism in central nervous system of post-stroke depression animals.