Myslivecek J, Barcal J, Hassmannová J, Zahlava J, Zalud V
Institute of Pathophysiology, Charles University Medical Faculty Plzen, Czech Republic.
Neuroscience. 1997 Aug;79(3):659-69. doi: 10.1016/s0306-4522(97)00029-8.
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.
考虑到我们之前关于多巴胺和一氧化氮对大鼠新生儿抑制性学习和记忆影响的研究结果,在本实验范式中研究了这两种分子的相互作用。将多巴胺和作为一氧化氮合酶底物的L - 精氨酸溶液注入侧脑室后,大脑中多巴胺含量和一氧化氮生物利用度的增加均改善了学习和24小时记忆。多巴胺和L - 精氨酸联合应用产生了更大的改善。D1受体激动剂也以剂量依赖的方式增强了学习和记忆过程,而D1受体拮抗剂则具有相反的、同样剂量依赖的作用。多巴胺或D1受体激动剂与硝基 - L - 精氨酸一起给药,硝基 - L - 精氨酸是一种由于一氧化氮可用性降低而损害学习和记忆的一氧化氮合酶抑制剂,它与L - 精氨酸一样拮抗了硝基 - L - 精氨酸的作用。D1受体拮抗剂损害了学习和记忆,而L - 精氨酸使学习值恢复正常。多巴胺和D1受体激动剂对24小时记忆的影响是浓度依赖性的,它们的较高浓度显著提高了记忆保持指数。这些相互作用的具体机制有待在进一步实验中确定。