Influence of intracerebral administration of L-NAME in dorsal hippocampus (CA1) on WIN55, 212-2 induced state-dependent memory in the step-down passive avoidance test

Background and This study presents the effects of nitricoxide synthase inhibitor (L-NAME) on WIN55, 212-2 induced state-dependent memory of passive avoidance task, which were examined in mice. Mice were anesthetized with intra-peritoneal injection of ketamine hydrochloride, plus xylazine and then placed in a stereotaxic apparatus. Also, two stainless-steel annuals were placed 1 min above CA1. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intra-CA1 administration of WIN55, 212-2 (0.5 and 1 µg/mouse), dose-dependent decreased the memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 (1µg/mouse), was restored by pre-test administration with the same dose of drug (1μg/mouse, intra-CA1). Single intra-CA1 administration of L-NAME (0.3, 1 and 3 µg/mouse), 5 minute pre-test could not alter memory retrieval. Also, in animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 (1µg/mouse), pre-test intra-CA1 administration of L-NAME (0.3, 1 and 3 µg/mouse) 24 hours after training, could not restore memory retrieval. Furthermore, in animals which received both post-training (1µg/mouse) and pre-test injection of WIN55, 212-2 (1µg/mouse), the injection of L-NAME (3 µg/mouse, intra-CA1), 2 minute before pre-test administration decreased retrieval. These findings may demonstrate the involvement of NO in state-dependent memory induced by intra-CA1 administration of WIN55, 212-2.