INHIBITION OF NITRIC-OXIDE SYNTHASE DOES NOT IMPAIR SPATIAL-LEARNING

Nitric oxide (NO), a putative intercellular messenger in the CNS, may be involved in certain forms of synaptic plasticity and learning. This article reports a series of experiments investigating the effects of N-omega-nitro-L-arginine methyl ester (L-NAME) upon various forms of l earning and memory in the watermaze. L-NAME (75 mg/kg, i.p., sufficien t to bring about >90% inhibition of NO synthesis in brain) produced an apparent impairment in spatial learning when given to naive rats duri ng acquisition (3 d, six training trials per day). This impairment was dose related, stereoselective, and attenuated by coadministration of L-arginine. A second study showed that L-NAME did not affect the reten tion of a previously learned spatial task. In addition, in a visual di scrimination task, the rate at which criterion levels of performance w ere reached was unaffected by L-NAME. Thus, inhibition of NO synthase may cause a selective impairment of spatial learning without effect up on retention. However, analysis of the early training trials of the vi sual discrimination task revealed significantly elevated escape latenc ies in the L-NAME-treated rats, suggesting that inhibition of NO synth ase may have more general effects. As normal rats learn the spatial ta sk very rapidly, the possibility arises that the apparent deficit in l earning is due to a disruption of some process other than learning per se. A further series of experiments investigated this possibility. L- NAME was found not to impair the learning of a new platform position i n the same spatial environment. Surprisingly, L-NAME also had no effec t on spatial learning in a second watermaze located in a novel spatial environment by rats well practiced with all aspects of watermaze trai ning. Finally, L-NAME had no effect on spatial learning in naive rats trained with just one trial per day. Thus, systemic injection of an NO synthase inhibitor impairs behavioral performance in two tasks during their initial acquisition, but the basis of this functional disruptio n is unlikely to be due to any direct effect upon the mechanisms of sp atial learning.