Developmental study on anti-dementia drugs by using neuropeptides related to memory disturbance

研究了μ-阿片受体激动剂内吗啡肽-1和-2对短期和长期记忆的影响。此外，本研究旨在寻找新的治疗痴呆症的药物。μ-阿片受体拮抗剂β-funalcumamine可显著拮抗内吗啡肽引起的短、长时记忆障碍。μ1阿片受体拮抗剂纳洛嗪对内吗啡肽-1引起的短期记忆障碍有明显改善作用，但对内吗啡肽-2引起的短期记忆障碍无明显改善作用。纳洛嗪、胆碱酯酶抑制剂或毒扁豆碱可改善长时记忆障碍。多巴胺D2受体激动剂RU 24213对内吗啡肽引起的短、长时记忆障碍无明显影响，多巴胺D2受体拮抗剂（-）-舒必利可显著对抗内吗啡肽引起的短、长时记忆障碍。上述结果表明，μ1-阿片受体、多巴胺D2受体和胆碱能神经传递在内吗啡肽引起的记忆障碍中起主要作用。此外，μ1-阿片受体拮抗剂可能用作新型抗痴呆药物。

The effects of the μ-opioid receptor agonists endomorphin-1 and -2 on short- and long-term memory were examined. In addition, the present study was designed to find novel therapeutic drugs for dementia. The μ-opioid receptor antagonist β-funaltrexamine significantly antagonized the endomorphins-induced disturbance of short- and long-term memory. Although the disturbance of short-term memory with endomorphm-1 was significantly improved by the μ1-opioid receptor antagonist naloxonazine, such drug was without any significant effects on the endomorphin-2-induced disturbance of short-term memory. Naloxonazine and the cholmesterase inhibit or physostigmine ameliorated the disturbance of long-term memory. The dopamine D2 receptor agonist RU24213 did not significantly influence the disturbance of short- and long-term memory induced by endomorpnms, the dopamine D2 receptor antagonist (-)-sulpiride significantly antagonized the endomorphins-induced disturbance of short- and long-term memory. From the above results, μ1-opioid receptor, dopamine D2 receptor and cholinergic neurotransmission play a major role in the memory disturbance with endomorpnins. Furthermore, it is possible that μ1-opioid receptor antagonists are useful as novel anti-dementia drugs.