Activation of hippocampal nitric oxide and calcium/calmodulin-dependent protein kinase II in response to Morris water maze learning in rats.

This study investigates the interactive roles of nitric oxide (NO) and CaM-kinase II (calcium/calmodulin-dependent protein kinase II) in Morris water maze learning. In Experiment I, experimental rats received 5 days of training on a Morris water maze, where the controls were trained in the water maze with no spatial cue condition or were trained via a visually guided landmark condition. The experimental rats showed improvement in their rate of spatial learning in the water maze. The escape latencies were significantly correlated with the Ca2+-independent activity of the hippocampal CaM-kinase II. Moreover, there was a significant increase in the endogenous phosphorylation of neuronal NOS and CaM-kinase II in the experimental group when compared to the controls. The intra-hippocampal infusion of 7-NI, KN-93, or AP5 did disrupt water maze learning. SDS-PAGE analysis showed that these drugs significantly depressed phosphorylation of hippocampal NOS. The Ca2+-independent activity of hippocampal CaM-kinase II was significantly lower in the KN-93 or the AP5 infused group when compared to the controls. Although these depressed activities were not reversed by the infusion of NO donor (sodium nitroprusside, SNP), the rats' water maze learning behavior were ameliorated significantly. These results, taken together, indicate that the NOS activation is essential for water maze learning, which may be triggered via the CaM-kinase II activation in hippocampus.