DOPAMINE D-1 RECEPTOR LIGANDS MODULATE COGNITIVE PERFORMANCE AND HIPPOCAMPAL ACETYLCHOLINE-RELEASE IN MEMORY-IMPAIRED AGED RATS
DOPAMINE D-1 RECEPTOR LIGANDS MODULATE COGNITIVE PERFORMANCE AND HIPPOCAMPAL ACETYLCHOLINE-RELEASE IN MEMORY-IMPAIRED AGED RATS
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DOI：
10.1016/0306-4522(95)00319-e
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发表时间：
1995-12-01
期刊：
影响因子：
3.3
通讯作者：
QUIRION, R
中科院分区：
文献类型：
--
作者：
HERSI, AI;ROWE, W;QUIRION, R
本研究探讨了D-1药物对老年记忆障碍动物学习能力的调节作用。首先通过定量放射自显影检查D-1/[H-3]SCH 23390受体的水平，以确定这些动物的认知缺陷是否与这些受体水平的改变有关。[H-3] sch23390结合在任何被检查的大脑区域中，在年轻和老年记忆未受损动物和老年记忆受损动物之间都没有观察到显著差异。然而，D-1药物可以调节衰老大鼠的认知缺陷。D-1激动剂SKF 38393和SKF 81297 （3.0 mg/kg, i.p）显著缩短了Morris水迷宫中寻找隐藏平台的潜伏期，反映了认知功能的改善，而D-1拮抗剂SCH 23390 （0.05 mg/kg, i.p）总体上没有显著作用。此外，D-1激动剂SKF 38393增加，而拮抗剂抑制体内海马乙酰胆碱释放。综上所述，这些结果表明在老年记忆受损大鼠中存在功能性海马乙酰胆碱-多巴胺相互作用。更重要的是，衰老受损大鼠的认知缺陷可以通过刺激D-1受体来减轻，因此提出了一种缓解衰老大脑认知缺陷的替代方法。
The possible modulation by D-1 drugs of learning abilities of a population of aged memory-impaired animals was investigated in the present study. The level of D-1/[H-3]SCH 23390 receptors was first examined by quantitative autoradiography to ascertain if cognitive deficits seen in these animals could be related to alterations in the levels of these receptors. No significant differences in [H-3]SCH 23390 binding were observed in any of the brain areas examined between young, and aged memory-unimpaired and aged memory-impaired animals. However, the cognitive deficits of the aged-impaired rats were modulated by D-1 drugs. The D-1 agonists SKF 38393 and SKF 81297 (3.0 mg/kg, i.p.) significantly reduced the latency period to find a hidden platform in the Morris Water Maze, reflecting improved cognitive functions, while the D-1 antagonist SCH 23390 (0.05 mg/kg, i.p.) had no overall significant effect. Moreover, the D-1 agonist SKF 38393 increased, whereas the antagonist inhibited, in vivo hippocampal acetylcholine release.Taken together, these results suggest that functional hippocampal acetylcholine-dopamine interactions exist in aged memory-impaired rats. More importantly, the cognitive deficits seen in the aged-impaired rats can be attenuated by stimulations of D-1 receptors, hence suggesting an alternative approach to alleviate the cognitive deficits seen in the aged brain.