Taking into account our previous results on dopamine and nitric oxide effects on neonatal inhibitory learning and memory in rats, the mutual interactions of the two molecules were studied in this experimental paradigm. Both increased dopamine content and nitric oxide bioavailability in the brain after application of dopamine and L-arginine as substrate for nitric oxide synthase solutions into lateral cerebral ventricles improved learning and 24 h memory.
Joint application of dopamine and L-arginine yielded still more improvement. Learning and memory processing were dose dependently enhanced by D1 receptor agonists as well, whereas D1 receptor antagonists had an opposite and also dose-dependent effect.
Dopamine or D1 receptor agonists administered together with nitro-L-arginine, a nitric oxide synthase inhibitor that impaired learning and memory due to a decreased nitric oxide availability, antagonized the effect of nitro-L-arginine, as did L-arginine. D1 receptor antagonists impaired both learning and memory, and L-arginine rendered learning values normal.
The dopamine and D1 receptor-agonist effect on 24 h memory was concentration dependent, and their higher concentrations substantially increased the retention indexes. The intimate mechanisms of these interactions are to be identified in further experiments.