Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task.

Impaired performance of alpha7 nicotinic receptor knockout mice in the five-choice serial reaction time task.
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DOI:
10.1007/s00213-006-0549-2
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发表时间:
2006-12
期刊:
影响因子:
3.4
通讯作者:
Stolerman, I. P.
Stolerman, I. P.
中科院分区:
医学3区
文献类型:
--
作者:
Hoyle, E.;Genn, R. F.;Fernandes, C.;Stolerman, I. P.

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尼古丁受体与注意力表现有关。尼古丁可以提高动物和人类的注意力,但对相关受体亚型的了解非常有限。目的是研究α7受体在小鼠注意力表现和尼古丁影响中的作用。将尼古丁受体α7亚基编码基因缺失小鼠和野生型对照小鼠进行5项连续反应时间任务训练,并在不同参数条件下提供食物强化物。尼古丁的剂量范围为(0.001-1.0 mg/kg sc),包括那些据报道能提高注意力表现的剂量。最初α7−/−(敲除)小鼠的反应准确性较低,并产生更多的预期反应。在改变任务参数以减少反应时间并通过暂停惩罚预期(冲动)反应后,表现缺陷的模式发生了变化;α7−/−小鼠的遗漏误差增加,但准确性和预期反应处于正常水平。无论是在原始训练参数下还是在再训练后,尼古丁都没有改善任何表现指标;使用的最大剂量(1.0 mg/kg)对α7−/−和野生型小鼠的反应产生普遍损害。α7烟碱受体敲除小鼠的5-CSRTT功能受损,提示α7受体可能在注意加工中起作用。然而,确定一种评估尼古丁对小鼠注意力增强作用的方案可能需要进一步修改试验程序或使用不同的动物品系。
Nicotinic receptors have been implicated in attentional performance. Nicotine can improve attention in animals and humans, but knowledge about relevant receptor subtypes is very limited. The aim was to examine the role of α7 receptors in attentional performance of mice and in effects of nicotine. Mice with targeted deletion of the gene coding for the α7 subunit of nicotinic receptors and wild-type controls were trained on a five-choice serial reaction time task with food reinforcers presented under varying parametric conditions. Nicotine was administered in a range of doses (0.001–1.0 mg/kg sc), including those reported to enhance attentional performance. Initially the α7−/− (knockout) mice responded less accurately and made more anticipatory responses. After task parameters were altered so that the time allowed for responding was reduced and anticipatory (impulsive) responses were punished by a time-out, the pattern of performance deficits changed; there were increased omission errors in α7−/− mice but normal levels of accuracy and anticipatory responding. Nicotine did not improve any measure of performance, either with the original training parameters or after retraining; the largest dose used (1.0 mg/kg) produced a general impairment of responding in α7−/− and wild-type mice. α7 nicotinic receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a possible role for α7 receptors in attentional processing. However, identification of a protocol for assessing attention-enhancing effects of nicotine in mice may require further modifications of test procedures or the use of different strains of animal.
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