Inhibitory learning and memory in newborn rats influenced by nitric oxide.

The impact of nitric oxide on learning, memory processing and retrieval was studied in the neonatal rats. For comparison, spontaneous motor activity and changes of brain temperature were also studied after nitric oxide manipulations in identical age groups. The nitric oxide availability was either increased by a systemic or intracerebroventricular application of L-arginine, a substrate of nitric-oxide synthase, or decreased 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 weight, or in the amounts of 11 into both lateral cerebral ventricles. Intact and saline injected pups were used as controls. Spontaneous motor behavior of newborn pups were not unambiguously affected by nitric oxide, and the same applies to changes of brain and body temperature or heart rate. In no case any correlation with changes of learning and/or memory could be established. Learning was dose dependently impaired relative to controls by intraperitoneal application of nitroarginine. L-arginine only slightly decreased numbers of trials to both criteria and partially abolished the blocking effect of nitroarginine on nitric oxide synthase. With the use of intracerebroventricular injections the positive impact of L-arginine on learning became highly significant. In 24-h memory, intraperitoneal injections of L-arginine enhanced the retention indexes. The impairing effect of nitro-L-arginine significantly 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 availability in brain after intracerebroventricular application of these substances at 16 various post-learning intervals were assessed on memory processing and retrieval. A general enhancing effect of increased nitric-oxide supply on 24-h retention indexes was found through all studied intervals, which was not, however, monotonous, but several peaks appeared with application at 3, 6, 18 and 23.5 h after learning. On the other hand, the suppressive effect of NArg was not evident relative to saline before the 6-h post-learning injection delay. These results show 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 depends on its actual bioavailability in the brain and the stage of memory processing.