Influence of intracerebral administration of NO agents in dorsal hippocampus (CA1) on cannabinoid state-dependent memory in the step-down passive avoidance test

In the present study, the effects of nitric oxide agents on WIN55, 212-2 induced state-dependent memory of passive avoidance task were examined in mice. One-trial step-down paradigm was used for the assessment of memory retention in adult male NMRI mice. Post-training intra-CA1 administration of CB1 and CB2 receptor agonists, WIN55, 212-2 (0.25, 0.5 and 1 µg/mouse), dose-dependently decreased memory retrieval. The memory impairment induced by post-training administration of WIN55, 212-2 (1 µg/mouse) was restored by pre-test administration of the same dose of the drug (1 μg/mouse, intra-CA1), showing the WIN55, 212-2 state-dependent memory. Single intra-CA1 administration of l-arginine (0.3, 1 and 3 µg/mouse) or L-NAME (0.3, 1 and 3 µg/mouse), 5 min pre-test could not alter memory retrieval. On the other hand, in the animals in which retrieval was impaired due to post-training administration of WIN55, 212-2 (1 µg/mouse), pre-test intra-CA1 administration of l-arginine (1 and 3 µg/mouse), but not L-NAME (0.3, 1 and 3 µg/mouse) 24 h after training restored memory retrieval. Also, in the animals which received both post-training (1 µg/mouse) and pre-test injections of WIN55, 212-2 (1 µg/mouse), the injection of L-NAME (3 µg/mouse, intra-CA1), 2 min before pre-test administration decreased retrieval. Furthermore, in the animals under the influence of post-training administration of WIN55, 212-2 (1 µg/mouse), pre-test co-administration of non-effective doses of WIN55, 212-2 (0.25 µg/mouse) and l-arginine (0.3 and 1 µg/mouse), increased the restoration of memory by pre-test WIN55, 212-2. These findings may demonstrate the involvement of NO in state-dependent memory induced by intra-CA1 administration of WIN55, 212-2.