Ameliorative effects of a cognitive enhancer, T-588, on place learning deficits induced by transient forebrain ischemia in rats

Abstract In the present study, we investigated the effect of (1 R )-1-benzo[ b ]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-588), a newly synthesized cognitive enhancer, on place learning deficits in rats with damage selective to the hippocampal CA1 subfield induced by transient forebrain ischemia. Three weeks after the ischemic insult, T-588 was daily administered (0.3 or 3.0 mg/kg/day po). 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 ischemic rats without the treatment of T-588 displayed severe learning impairment in this task; their performance level was significantly inferior to that of the sham-operated rats. The treatment of T-588 improved dose-dependently the task performance in ischemic rats, although no apparent protective effects on ischemic damage were found histologically. These results suggested that T-588 has ameliorative effects on learning deficits induced by brain ischemia, which could be produced through enhancement of residual cognitive functions.