Effects of nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on spatial and cued leaning.

An investigation was made of the effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the acquisition and retention of two operantly conditioned discrimination tasks. Twenty Long-Evans rats were conditioned to approach one of two spatial locations that was either held constant across trials (spatial task) or was associated with a visual cue (illuminated lamp) that was randomly assigned to one of the locations on each trial (cued task). Rats were assigned to one of two treatment groups in which they received intraperitoneal injections of either NG-nitro-L-arginine methyl ester or saline approximately 2 h before sessions on each day of training. Analysis was made of the trial-by-trial performance in order to identify the characteristics of learning under each condition. Assessment of learning acquisition was based on the number of trials required to reach a criterion of 80% correct responses, whereas retention was assessed by the number of trials to criterion on each day after the criterion was initially reached. Analysis indicated that treatment groups did not differ significantly on acquisition or retention of either the spatial or cued task. These results indicate that inhibition of nitric oxide synthase does not interfere with the learning or retention of basic operant tasks that involve simple spatial or visual analysis. Whereas results from biochemical and physiological investigations have suggested an impact of nitric oxide synthase on behavioural function, behavioural investigations indicate a limited impact of nitric oxide synthase inhibition on learning and memory. Although these results do not discount the role of nitric oxide synthase in a hippocampal mechanism, they illustrate that behavioural analysis should be made in the context of multiple interacting neural systems. Viewed with previous behavioural research on the effects of NG-nitro-L-arginine methyl ester, these results indicate that nitric oxide synthase inhibition results in impairment of certain forms of learning whereas other forms are preserved.