Effects of LY231617 and angiotensin IV on ischemia-induced deficits in circular water maze and passive avoidance performance in rats.

The antioxidant LY231617 has previously been shown to offer significant protection against postischemic cell death in the hippocampus and corpus striatum of rats. The present results extend this observation by demonstrating a concomitant protection against the spatial memory deficits that accompany damage to the hippocampus, as measured by the circular water maze task. These animals were further tested for changes in associative memory by employing a passive avoidance conditioning task. No deficits in passive avoidance conditioning were measured among the 4-vessel occlusion animals treated with LY231617 or vehicle. However, the intracerebroventricular injection of angiotensin IV (Ang IV) immediately prior to foot-shock conditioning improved retention of the conditioned response during the subsequent 2-day period. These results suggest that LY231617 can offer considerable protection against global ischemia-induced cell death in the hippocampus with resulting preservation of spatial memory abilities. In addition, untreated animals that suffered cell losses in the hippocampus remained capable of responding to the facilitory effect of centrally administered Ang IV on a non-spatial memory task. The hypothesized mechanisms of the protection characteristics of LY231617, and the nootropic effect of Ang IV, are discussed.