The combination of memantine and galantamine improves cognition in rats: The synergistic role of the α7 nicotinic acetylcholine and NMDA receptors
The combination of memantine and galantamine improves cognition in rats: The synergistic role of the α7 nicotinic acetylcholine and NMDA receptors
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DOI：
10.1016/j.bbr.2016.07.023
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发表时间：
2016-10-15
影响因子：
2.7
通讯作者：
Popik, Piotr
中科院分区：
文献类型：
--
作者：
Nikiforuk, Agnieszka;Potasiewicz, Agnieszka;Popik, Piotr
美金刚和乙酰胆碱酯酶抑制剂（AChEI）的组合被用作改善阿尔茨海默病认知的治疗策略。在AChEI中，加兰他敏，其也是烟碱乙酰胆碱受体（nAChR）（包括α 7-nAChR）的正变构调节剂（PAM），可能是特别有益的。α 7-nAChR参与胆碱能系统和多巴胺能系统之间的相互作用。在本研究中，我们研究了α 7-nAChRs在这种药物组合的促认知作用中的潜在作用。采用注意定势转换任务（ASST）和新物体再认任务（NORT）评估大鼠的认知能力，发现美金刚和加兰他敏联合应用可促进大鼠的定势转换能力，逆转延迟性物体再认障碍。这些作用被α 7-nAChR拮抗剂methylylycaconitine阻断，表明观察到的认知增强是α 7-nAChR依赖性的。此外，美金刚与非活性剂量的选择性α 7-nAChR PAM、CCMI和PNU-120596的组合施用也以甲基利卡那汀依赖性方式改善ASST和NORT表现。我们的研究结果表明，美金刚胺，当与α 7-nAChRs的增强剂，可能是一种有效的策略，认知改善。(C)2016爱思唯尔B. V.保留所有权利。
The combination of memantine and acetylcholinesterase inhibitors (AChEIs) is used as a therapeutic strategy to improve cognition in Alzheimer's disease. Among AChEIs, galantamine, which is also a positive allosteric modulator (PAM) of nicotinic acetylcholine receptors (nAChRs), including alpha 7-nAChRs, may be particularly beneficial. The alpha 7-nAChR is involved in interactions between the cholinergic and glutamatergic systems. In the present study, we investigated the potential role of alpha 7-nAChRs in the pro cognitive effects of this drug combination. To this aim, cognitive performance in rats was assessed using the attentional set shifting task (ASST) and novel object recognition task (NORT).Co-administration of inactive doses of memantine with galantamine facilitated the rats' set-shifting performance and reversed delay-induced deficits in object recognition. These effects were blocked by the alpha 7-nAChR antagonist methyllycaconitine, suggesting that the observed cognitive enhancement is alpha 7-nAChR dependent. Moreover, combined administration of memantine with inactive doses of selective alpha 7-nAChRs PAMs, CCMI and PNU-120596, also improved ASST and NORT performance in a methyllycaconitine-dependent manner.Stimulation of alpha 7-nAChRs may underlie the pro-cognitive effects of combining memantine and galantamine. Our results suggest that memantine, when given with enhancers of alpha 7-nAChRs, may represent an effective strategy for cognitive improvement. (C) 2016 Elsevier B.V. All rights reserved.