Involvement of hippocampal nitric oxide in spatial learning in the rat

Nitric oxide (NO) is thought to be involved in synaptic plasticity contributing to learning and memory in several brain areas including the hippocampus. The hippocampus is believed to have a critical role in the processing of spatial information. But, data on the role of hippocampal NO in spatial learning are not consistent. So the effect of NO synthase (NOS) inhibition in the CA1 region of rat hippocampus on spatial localization was investigated in the Morris water maze (MWM). Male albino Wistar rats cannulated in their CA1 region received bilateral injections of vehicle (saline) or Nω-nitro-l-arginine methyl ester (l-NAME), a NOS inhibitor (50, 100 and 200 μg/0.5 μl) through the cannulae 30 min before training each day. Animals were subjected to 5 days of training in the MWM; 4 days with the invisible platform to test spatial learning and the 5th day with the visible platform to test motivation and sensorimotor coordination. The results showed dose-dependent increases (p < 0.001) in escape latency, traveled distance, heading angle, and dose-dependent decreases (p < 0.01) in target quadrant entries in l-NAME-received groups as compared to the control group. This impairment was reversed by co-administration of mole-equivalent doses of l-arginine (l-Arg), the NO precursor. l-Arg alone at the dose of 129.2 μg, increased heading angle (p < 0.01) with no effect on other parameters. On the basis of the present data, it is concluded that processes mediated by NO synthesis in the hippocampus are essentially involved in spatial learning.