INHIBITORY LEARNING AND MEMORY IN NEWBORN RATS INFLUENCED BY NITRIC-OXIDE

The impact of nitric oxide on learning, memory processing and retrieva l was studied in the neonatal rats. For comparison, spontaneous motor activity and changes of brain temperature were also studied after nitr ic oxide manipulations in identical age groups. The nitric oxide avail ability was either increased by a systemic or intracerebroventricular application of L-arginine, a substrate of nitric-oxide synthase, or de creased by nitro-L-arginine, its inhibitor. L-arginine, 20 mM or nitro -l-arginine, 10 or 5 mM were given intraperitoneally, 1 ml/100 g weigh t, or in the amounts of 11 into both lateral cerebral ventricles. Inta ct and saline injected pups were used as controls. Spontaneous motor b ehavior of newborn pups were not unambiguously affected by nitric oxid e, and the same applies to changes of brain and body temperature or he art rate. In no case any correlation with changes of learning and/or m emory could be established. Learning was dose dependently impaired rel ative to controls by intraperitoneal application of nitroarginine. L-a rginine only slightly decreased numbers of trials to both criteria and partially abolished the blocking effect of nitroarginine on nitric ox ide synthase. With the use of intracerebroventricular injections the p ositive impact of L-arginine on learning became highly significant. In 24-h memory, intraperitoneal injections of L-arginine enhanced the re tention indexes. The impairing effect of nitro-L-arginine significantl y increased with delaying after-learning application intervals, being more pronounced at the 3-h than at 0-h interval. Here also, its effect was partially abolished by L-arginine. Effects of nitric-oxide availa bility in brain after intracerebroventricular application of these sub stances at 16 various post-learning intervals were assessed on memory processing and retrieval. A general enhancing effect of increased nitr ic-oxide supply on 24-h retention indexes was found through all studie d intervals, which was not, however, monotonous, but several peaks app eared with application at 3, 6, 18 and 23.5 h after learning. On the o ther hand, the suppressive effect of NArg was not evident relative to saline before the 6-h post-learning injection delay. These results sho w that nitric oxide exerts a considerable central modulatory effect on learning, memory processing and retrieval at the very early postnatal period of the rat. The efficiency of nitric-oxide manipulations depen ds on its actual bioavailability in the brain and the stage of memory processing.