Deficits in working memory following inhibition of hippocampal nitric oxide synthesis in the rat.

In order to elucidate the roles of hippocampal nitric oxide (NO) synthesis in working and reference memory performance of rats, the effects of intrahippocampal injections of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), on this behavior were examined with a three-panel runway task. In the working memory task, L-NAME, injected bilaterally at 10 and 32 micrograms/side into the dorsal hippocampus, significantly increased the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points). This effect of intrahippocampal L-NAME (32 micrograms/side) on working memory was attenuated by concurrent injection of 100 micrograms/side L-arginine, the precursor of NO. Intrahippocampal injection of the inactive isomer D-NAME at doses up to 32 micrograms/side had no effect on the number of working memory errors. In the reference memory task, neither L-NAME nor D-NAME affected the number of errors when injected into the hippocampus at doses up to 32 micrograms/side. These results suggest that processes mediated by NO synthesis in the hippocampus are involved in working memory, but not in reference memory.