Attentional effects of nicotinic agonists in rats
Attentional effects of nicotinic agonists in rats
复制标题
DOI：
10.1016/s0028-3908(03)00099-6
复制
发表时间：
2003-06-01
影响因子：
4.7
通讯作者：
Stolerman, P
中科院分区：
文献类型：
--
作者：
Hahn, B;Sharples, CGV;Stolerman, P
尼古丁可以增加刺激检测，反应率和速度在五个选择系列反应时间任务，啮齿动物的注意力测试。在本实验中，在相同的程序中比较了具有不同药理学特征的其他四种烟碱激动剂。地棘蛙素的反应特征与之前使用尼古丁获得的反应特征相似，因为反应准确性增强，遗漏错误和正确反应潜伏期减少。ABT-4 T8在测试的前10分钟短暂增加了准确性，并减少了反应延迟。异戊烯酮引起剂量相关的准确性增加，但对遗漏或反应潜伏期没有影响。这种对反应率或速度相关指标无影响的情况可能与其先前报告的与尼古丁相比释放多巴胺的能力降低有关。α 7-激动剂AR-RT 7779对任何测量都没有影响，表明这种受体亚型可能不介导对注意力的烟碱效应。在针对α 4 β 2、α 7、α 3 β 4和α 3 β 2 * nAChR亚型的竞争结合测定中确定的化合物的亲和力常数不能解释观察到的差异行为效应。它们对nAChR亚型的功能功效的差异可能是负责任的。注意力表现和反应速率和速度可以通过烟碱激动剂选择性地调节的发现对于开发具有与尼古丁相似的治疗特性但具有减少的不良作用的药物是令人鼓舞的。(C)2003爱思唯尔科技有限公司版权所有。
Nicotine can increase stimulus detection, response rate and speed in the five-choice serial reaction time task, a rodent test of attention. In the present experiments, four other nicotinic agonists with different pharmacological profiles were compared in the same procedure. The response profile of epibatidine resembled that previously obtained with nicotine in that response accuracy was enhanced and omission errors and correct response latency decreased. ABT-4T8 transiently increased accuracy in the first 10 min of test sessions and reduced response latency. Isoarecolone caused a dose-related increase in accuracy, but had no effect on omissions or response latency. This absence of effects on response rate- or speed-related measures may be related to its previously reported reduced ability to release dopamine as compared with nicotine. The alpha7-agonist AR-RT7779 was without effect on any measure, indicating that this receptor subtype may not mediate nicotinic effects on attention. Affinity constants of compounds, determined in competition binding assays targeting the alpha4beta2, alpha7, alpha3beta4 and alpha3beta2* nAChR subtypes, could not explain the differential behavioural effects observed. Differences in their functional efficacy at nAChR subtypes may instead be responsible. The finding that attentional performance and response rate and speed can be selectively modulated by nicotinic agonists is encouraging for the development of drugs with therapeutic properties similar to those of nicotine but with reduced unwanted effects. (C) 2003 Elsevier Science Ltd. All rights reserved.