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Introduction: There are evidences showing the role of nitric oxide in the opiate reward properties. The role of nitric oxide signaling pathway as an intracellular mechanism on augmentation of long term potentiation in hippocampal CA1 area of rats is also confirmed. It has been also reported that oral morphine dependence facilitates formation of spatial learning and memory via activation of NMDA receptors located in hippocampal CA1 area of rats. The effect of nitric oxide within hippocampal CA1 area on the spatial learning and memory processes in morphine dependent rats is unclear. Methods: 33 N-MRI male rats (250-350 g) were divided into 4 experimental groups. Two cannulae were stereotaxically implanted bilaterally into hippocampal CA1 area. After 5 days recovery, animals received morphine sulfate or sucrose for 30 consecutive days in drinking water. Morris water maze (MWM) studies were performed from day 26 to 30. In this period animals received bilateral intra-hippocampal CA1 injection of 3μg/ 2 μl L-NAME (NOS inhibitor) or 2 μl saline (1 μl/site), 1 min before daily experimentation. Spatial learning and memory parameters were subjected to analysis of variance (ANOVA). Results: Morphine dependence facilitated spatial learning and memory in rats. This effect was inhibited with local administration of L-NAME in hippocampal CA1 area. Conclusion: Activation of intracellular NO signaling pathway in the pyramidal cells of hippocampal CA1 area may involve in facilitating spatial learning and memory in morphine dependent rats.

Keywords: Nitric oxide, morphine, hippocampal CA1, spatial learning and memory, rat

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