Ameliorative effects of tamolarizine on place learning impairment induced by transient forebrain ischemia in rats

In the present study we investigated the effect of (+/-)-1-(3, 4-dimethoxyphenyl)-2-(4-diphenylmethylpiperazinyl) ethanol dihydrochloride (tamolarizine), a calcium entry blocker, on place learning impairment in rats with damage selective to the hippocampal CA1 subfield induced by transient forebrain ischemia. Tamolarizine was administered (40 mg/kg) immediately after 15-min brain ischemia. Place learning was tested in a task in which the rat was required to alternatively visit two places located diametrically opposite each other in an open field. The ischemia+saline group showed severe learning impairment in this task; their performance level was significantly inferior to that of the sham-operated group through the test period (30 days). Although the ischemia+tamolarizine group showed slight impairment of place learning during the course of this test, they later reached almost the same performance level as the sham-operated group. Selective neuronal loss in the CA1 subfield was much less in the ischemia+tamolarizine group than in the ischemia+saline group. These results indicate that tamolarizine treatment protects the hippocampus from ischemic brain damage and ameliorates place learning impairment.