A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats
A-412997, a selective dopamine D4 agonist, improves cognitive performance in rats
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DOI：
10.1016/j.pbb.2005.08.002
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发表时间：
2005-09-01
影响因子：
3.6
通讯作者：
Fox, GB
中科院分区：
文献类型：
--
作者：
Browman, KE;Curzon, P;Fox, GB
最近开发的一种高选择性多巴胺D-4受体激动剂A-412997（2-（3 '，4'，5 '，6'-tetrahydro-2 'H-[2，4'] bipyridinyl-1 'yl）-N-m-tolyl-acetamide），为系统研究多巴胺D-4受体在中枢神经系统中的作用提供了一种药理学工具。这些当前研究评估了A-412997在ADHD（自发性高血压大鼠幼崽中进行5次重复获得抑制性回避试验）和短期记忆（社会识别）大鼠模型中的潜在认知增强特性，并与选择性较低的多巴胺D-4受体激动剂进行了比较受体激动剂PD 168077和CP 226269。A-412997在两种模型中均显示出显著的剂量依赖性疗效。PD 168077在5次试验抑制性回避模型中反复改善了获得，但在任何测试剂量下均未达到显著性，尽管观察到显著改善的社会识别（尽管效力低于A-412997）。CP 226269在5次试验抑制性回避模型中显示出显著增强。这些结果支持多巴胺D4受体亚型在认知中的作用。(c)2005年爱思唯尔公司All rights reserved.
The recent development of a highly selective dopamine D-4 receptor agonist, A-412997 (2-(3',4',5',6'-tetrahydro-2'H-[2,4'] bipyridinyl-1'yl)-N-m-tolyl-acetamide), has provided a pharmacological too] with which to conduct systematic investigations into the putative role for dopamine D-4 receptors in the central nervous system. These present studies evaluated the potential cognitive enhancing properties of A-412997 in rat models of ADHD (5-trial repeated acquisition inhibitory avoidance in Spontaneous Hypertensive Rat pups) and short-term memory (Social Recognition), in comparison with the less selective dopamine D-4 receptor agonists PD168077 and CP226269. A-412997 showed significant dose-dependent efficacy in both models. PD168077 repeatedly improved acquisition in the 5-trial inhibitory avoidance model but failed to reach significance at any dose tested, although significantly improved social recognition was observed (albeit less potent than A-412997). CP226269 showed a significant enhancement in the 5-trial inhibitory avoidance model. These results support a role for the dopamine D4 receptor subtype in cognition. (c) 2005 Elsevier Inc. All rights reserved.