Inhibition of the endothelial isoform of nitric oxide synthase impairs long-term memory formation in the chick

Previous studies with general inhibitors of nitric oxide synthase have yiel ded variable and contradictory results with respect to their effects on mem ory. This may have been due to differential effects of blocking the various isoforms of this enzyme. We show that day-old chicks trained on a single-t rial passive-avoidance task suffered, significant memory loss from similar to 40 min post-training following post-training intracranial administration of a potent inhibitor of eNOS. Administration of a specific nNOS or iNOS i nhibitor at the same time had no effect on retention, although a role for e ither of these isoforms when administered at a different time after learnin g has yet to be fully investigated The onset of memory loss following eNOS inhibition is the same as observed following general NOS inhibition, which suggests that amnestic effects observed. in previous studies using nonspeci fic inhibitors may be attributable to blocking the function of eNOS. The fi ndings indicate that eNOS may play a role in memory formation for this task , which is at least distinct from any role that may be played by nNOS.