Combination of rimonabant and donepezil prolongs spatial memory duration.
Combination of rimonabant and donepezil prolongs spatial memory duration.
复制标题
利莫那班和多奈哌齐的组合可延长空间记忆持续时间。
DOI：
10.1038/sj.npp.1301297
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Lichtman,AronH
中科院分区：
文献类型：
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作者：
Wise,LauraE;Iredale,PhilipA;Stokes,ReneJ;Lichtman,AronH
大麻素1 （cb1）受体拮抗剂/逆向激动剂利莫那班和选择性非竞争性乙酰胆碱酯酶抑制剂多奈哌齐在各种动物记忆模型中改善表现的观察结果表明，这些神经化学系统在认知中起着不可或缺的作用。目前的研究测试了这些药物单独或联合使用是否会延长空间记忆的持续时间。大鼠采用两阶段径向臂迷宫训练，包括获取和检索测试，两者之间间隔18 h。每种药物分别在习得阶段前30分钟、习得阶段后30分钟或检索测试前30分钟给药，以评估习得/巩固、巩固和检索记忆过程。在习得阶段之前，而不是在习得之后或检索之前，给予利莫那班或多奈哌齐，会导致检索测试中错误数量的显著减少。亚阈剂量的利莫那班和多奈哌齐联合使用，单独给药时对表现没有明显影响，但增强了记忆。这些结果表明，延迟径向臂迷宫任务足够敏感，可以检测这些药物的记忆增强作用。此外，这些研究结果表明，亚阈剂量利莫那班和多奈哌齐联合使用可以改善记忆，并可能代表一种治疗神经退行性疾病相关认知缺陷的新方法。
The observations that the cannabinoid 1 (CB 1) receptor antagonist/inverse agonist, rimonabant, and the selective noncompetitive inhibitor of acetylcholinesterase (AChE), donepezil, improve performance in a variety of animal memory models, suggest that these neurochemical systems play integral roles in cognition. The present study tested whether each of these agents administered alone or in combination will prolong the duration of spatial memory. Rats were trained in a two-phase radial-arm maze procedure, consisting of acquisition and retrieval tests, which were separated by an 18 h delay. Each drug was administered 30 min before the acquisition phase, immediately after the acquisition phase, or 30 min before the retrieval test to assess acquisition/consolidation, consolidation, and retrieval mnemonic processes, respectively. Rimonabant or donepezil administered before the acquisition phase, but not immediately after acquisition or before retrieval, led to a significant decrease in the number of errors committed during the retrieval test. Combined administration of subthreshold doses of rimonabant and donepezil that had no discernable effects on performance when given alone, enhanced memory. These results taken together demonstrate that the delay radial-arm maze task is sufficiently sensitive to detect memory enhancing effects of these drugs. Moreover, these findings suggest that combined administration of subthreshold doses of rimonabant and donepezil can improve memory and may represent a novel approach to treat cognitive deficits associated with neurodegenerative disorders.