Intrahippocampal administration of the NO synthase inhibitor L-NAME prevents working memory deficits in rats exposed to transient cerebral ischemia.

A 5-min period of cerebral ischemia increased the number of errors in a working memory task with three-panel runway paradigm, while it had no effect on reference memory errors. The nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), infused into the bilateral dorsal hippocampus at 100 micrograms/side immediately after blood flow reperfusion, significantly reduced the increase in working memory errors expected to occur 24 h after 5 min of ischemia. Intrahippocampal administration of the inactive isomer D-NAME at 100 micrograms/side immediately after reperfusion had no effect on the increase in working memory errors in the ischemic rats. These findings suggest that the mechanism mediated by hippocampal NO synthesis during the early reperfusion phase contributes to the postischemic impairment of working memory.