The nitric oxide synthesis inhibitor L-NAME facilitates associative learning.

1. Nitric oxide has been suggested to play an important role in synaptic plasticity and in learning. 2. The authors examined the effects of NW-nitro-L-arginine methyl ester, a competitive and enantiomeric specific inhibitor of nitric oxide synthase, on classical conditioning of the rabbit's nictitating membrane response. 3. It was found that L-NAME significantly enhanced the acquisition of conditioned responses. 4. The enhanced conditioned responses were not due to a sensitization of the conditioned and unconditioned reflexes or to changes in baseline levels of responding. 5. The dose and route of administration of L-NAME employed in this study had no effect on blood pressure. 6. These results suggest that nitric oxide normally functions as a tonic inhibitory modulator of associative learning and that procedures aimed at decreasing its production may provide a novel approach for improving learning.