THE ROLE OF NITRIC-OXIDE IN PASSIVE-AVOIDANCE LEARNING

The role of nitric oxide on passive avoidance learning was studied by administering L-arginine or D-arginine to male rats in a passive avoid ance paradigm. L-Arginine administered into the lateral brain ventricl e at a dose of 1.25 mu g showed a tendency to increase the passive avo idance latency, and 2.5 mu g exerted almost maximal action, but the ac tion gradually increased still further up to 20 mu g tested. D-Arginin e had no action. Peripheral administration (intraperitoneal) of L-argi nine facilitated the consolidation of passive avoidance learning in a dose-dependent manner. A significant increase in passive avoidance res ponse was obtained following an injection of 100 mg/kg L-arginine. Whe n L-arginine was given i.c.v. with a selected dose of 5 mu g, 30 min p rior to a learning trial, the latency of the passive avoidance respons e was likewise lengthened. However, when L-arginine was given 30 min b efore the 24-hr testing (retrieval), it was ineffective. It was also i neffective when given 6 hr after the training trial. However, when L-a rginine was administered immediately following the training trial, the action in improving the consolidation could be detected 6 hr after th e training trial. Nitro-L-arginine, which blocks nitric oxide synthase , can also block the facilitation of consolidation caused by the nitri c oxide donor L-arginine. The nitric oxide synthase inhibitor per se i n different doses had no action on the learning of a passive avoidance task. The results indicate that nitric oxide is able to facilitate th e learning and consolidation of memory in a passive avoidance paradigm , but it is ineffective in retrieval processes. The results also sugge st that, under the experimental circumstances used, nitric oxide is in volved only in the facilitated learning and memory processes caused by pharmacological effect of L-arginine, and not involved in normal lear ning processes. (C) 1998 Elsevier Science Ltd. All rights reserved.