Hiramatsu M, Kameyama T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Methods Find Exp Clin Pharmacol. 1998 Sep;20(7):595-9. doi: 10.1358/mf.1998.20.7.485724.
The role of kappa-opioid receptor agonists on learning and memory is controversial. In this review, the effects of dynorphin A (1-13) and U-50,488H on learning and memory impairments in mice and rats are summarized. Muscarinic cholinergic antagonists and a nicotinic cholinergic antagonist significantly impaired learning and memory in various behavioral tests. Administration of dynorphin A (1-13) or U-50,488H reversed the impairment of learning and memory. U-50,488H completely blocked the decrease in acetylcholine release induced by mecamylamine, while it only partially blocked the increase of acetylcholine induced by scopolamine. The antagonistic effect of U-50,488H was abolished by pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist. Dynorphin A (1-13) and U-50,488H did not affect the impairment of learning and memory induced by the blockade of NMDA-receptors by dizocilpine ((+)-MK-801. These results suggest that kappa-opioid receptor antagonist reverses the impairment of learning and memory induced by the blockade of cholinergic transmission and abolishes the decrease of acetylcholine release via the kappa-opioid receptor-mediated neuronal system.
κ-阿片受体激动剂对学习和记忆的作用存在争议。在本综述中，总结了强啡肽A（1-13）和U-50,488H对小鼠和大鼠学习记忆障碍的影响。毒蕈碱型胆碱能拮抗剂和烟碱型胆碱能拮抗剂在各种行为测试中均显著损害学习和记忆。给予强啡肽A（1-13）或U-50,488H可逆转学习和记忆障碍。U-50,488H完全阻断了美加明诱导的乙酰胆碱释放减少，而仅部分阻断了东莨菪碱诱导的乙酰胆碱增加。选择性κ-阿片受体拮抗剂nor-naltorphimine预处理可消除U-50,488H的拮抗作用。强啡肽A（1-13）和U-50,488H不影响地卓西平（(+)-MK-801）阻断NMDA受体诱导的学习和记忆障碍。这些结果表明，κ-阿片受体拮抗剂可逆转胆碱能传递阻断诱导的学习和记忆障碍，并通过κ-阿片受体介导的神经元系统消除乙酰胆碱释放的减少。
