CHRONIC ADMINISTRATION OF L-NAME IN DRINKING-WATER ALTERS WORKING-MEMORY IN RATS

To examine the role of nitric oxide (NO) in the maintenance of working memory of rats, the effects of chronic administration (in drinking wa ter) of the NO synthase inhibitor, N(omega)nitro-L-arginine methyl est er (L-NAME), on this behavior was examined with a simple test of remem bering recently explored objects. Unlike other working memory tasks th at require a subject to perform for a reward such as food or water or to avoid shock, our task measured spontaneous exploration of novel and familiar objects and has been described as a ''pure'' working memory task [9]. Normal subjects spend significantly more time in contact wit h new environmental components and less time with familiar objects. A subject that extensively reexplores a stimulus with which it has previ ous experience is presumed to exhibit some memory loss associated with the object. Memory changes were evaluated by measuring the relative t ime subjects explored familiar versus new stimulus objects. Rats (n = 15) that chronically drank L-NAME (approximate to 90 mg/kg/day) for 14 days spent significantly less time exploring a novel object than did rats in = 13) that drank only tap water (p <.05). This effect of L-NAM E was abolished by concurrent administration of L-Arginine (approximat e to 4.5 g/kg/day). Total object exploration was not affected by our d rug treatments, suggesting that our object discrimination task is not activity dependent. These data are consistent with the hypothesis that NO is required for some forms of working memory.