ABSTRACT
AIM:To investigate the regulatory effects and underlying molecule-mechanism of clonidine on learning and memory in rats with chronic cerebral ischemia.METHODS: Sprague-Dawley rats(n=45)were randomly divided into sham-operation group,cerebral ischemia model group and clonidine group,15 rats in each group.The chronic cerebral ischemia rat model was established by right middle cerebral artery occlusion for 2 h and reperfusion for 30 d. Clonidine was administrated by i.g.for 7 days in clonidine group.The ability of spatial reference memory of the rats with cerebral ischemia was tested by Morris water maze.The protein levels of extracellular signal-regulated kinase 1/2(ERK1/2),phosphorylated ERK1/2(p-ERK1/2), cAMP-response element binding protein(CREB)and phosphorylated CREB (p-CREB)were determined by immunohistochemistry and Western blot.RESULTS:The results of Morris water maze test showed that compared with the sham-operation group,the ability of spatial reference memory was obviously impaired in the cerebral ischemia model group.Compared with the cerebral ischemia model group,the ability of spatial reference memory in the clonidine group were improved.Compared with the sham-operation group, the protein levels of p-ERK1/2 and p-CREB in hippocampus were increased in model group(P<0.01).Compared with the cerebral ischemia model group,the protein levels of p-ERK1/2 and p-CREB in hippocampus were decreased in the clonidine group(P<0.01).CONCLU-SION:Clonidine improves the learning and memory abilities of the rats with cerebral ischemia, and ERK1/2 and CREB are involved in this process.