Hoyle E, Genn R F, Fernandes C, Stolerman I P
Section of Behavioural Pharmacology, Institute of Psychiatry PO49, King's College London, De Crespigny Park, London, SE5 8AF, UK.
Psychopharmacology (Berl). 2006 Dec;189(2):211-23. doi: 10.1007/s00213-006-0549-2. Epub 2006 Sep 20.
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 alpha7 receptors in attentional performance of mice and in effects of nicotine.
Mice with targeted deletion of the gene coding for the alpha7 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 alpha7(-/-) (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 alpha7(-/-) 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 alpha7(-/-) and wild-type mice.
alpha7 nicotinic receptor knockout mice are impaired in performance of the 5-CSRTT, suggesting a possible role for alpha7 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.
烟碱型受体与注意力表现有关。尼古丁可改善动物和人类的注意力，但关于相关受体亚型的了解非常有限。
旨在研究α7受体在小鼠注意力表现及尼古丁作用中的作用。
对靶向缺失烟碱型受体α7亚基编码基因的小鼠和野生型对照小鼠进行训练，使其在一种五选择连续反应时间任务中，在不同参数条件下给予食物强化物。以一系列剂量（0.001 - 1.0 mg/kg皮下注射）给予尼古丁，包括据报道可增强注意力表现的剂量。
最初，α7（-/-）（基因敲除）小鼠反应准确性较低且有更多预期反应。在改变任务参数，使反应时间减少且预期（冲动）反应通过暂停惩罚后，表现缺陷模式发生变化；α7（-/-）小鼠的遗漏错误增加，但准确性和预期反应水平正常。无论是在原始训练参数下还是再训练后，尼古丁均未改善任何表现指标；所使用的最大剂量（1.0 mg/kg）导致α7（-/-）和野生型小鼠的反应普遍受损。
α7烟碱型受体基因敲除小鼠在5 - CSRTT任务表现中受损，提示α7受体在注意力加工中可能发挥作用。然而，确定评估小鼠中尼古丁增强注意力作用的方案可能需要进一步修改测试程序或使用不同品系的动物。
