Objective To investigate the effects of nitric oxide (NO) on nicotinic acetylcholine receptor (nAChR)expression in prefrontal cortex and hippocampus and the ability of spatial learning and memory.Methods NO precursor L-arginine (L-Arg) 0.5 μmol/d (L-Arg group) or nitric oxide synthase (NOS) inhibitor Nω-nitro-L-arginine methylester (L-NAME) 5 μmol/d (L-NAME group) was intracerebroventricularly (i.c.v) administered in rats once daily for a succession of 7 days and the same amount of saline as control.The ability of spatial learning in Y-maze was tested after 12 h of the i.c.v administration at the last day, and memory test was taken 24 h later of the learning test.And then the levels of NO were tested using NO assay kit, the α7 nAChR expressions in the prefrontal cortex and hippocampus were examined using immunohistochemistry or Western blot.Results Compared to controls,the rats in L-Arg group took less electrical foot stimulation and errors to reach the learning standard and less errors during 30 stimulating times of memory test;Whereas, all indicators of the ability of learning and memory were increased in L-NAME group as compared with that in control group.The content of NO, and α7 nAChR-LI neurons with immunocytochemistry, or α7 nAChR protein with Western-blot in prefrontal cortex and hippocampus were all significantly increased in L-Arg group as compared with that in control group, whereas decreased in L-NAME groups as compared with that in control group.Conclusion These results indicated that multiple administration NO precursor L-Argcould increase the content of NO in central nervous system, and significantly increased the α7 nAChR expression of prefrontal cortex and hippocampus, and consequently enhanced the ability of learning and memory;Whereas, multiple administration of L-NAME led to lack of nitric oxide, and decreased the expression of α7 nA ChR in prefrontal cortex and hippocampus, so inhibited the ability of learning and memory.