Young Jared W, Finlayson Keith, Spratt Christopher, Marston Hugh M, Crawford Nicola, Kelly John S, Sharkey John
Fujisawa Institute of Neuroscience, Division of Neuroscience, University of Edinburgh, Edinburgh, UK.
Neuropsychopharmacology. 2004 May;29(5):891-900. doi: 10.1038/sj.npp.1300393.
In humans, nicotine has been shown to improve attention in both normal and impaired individuals. Observations in rats reflect some, but not all aspects of the nicotine-induced improvements in humans. To date these findings have not been replicated in mice. To examine the effect of nicotine on sustained attention in mice, we have established a version of the 5-choice serial reaction-time (5-CSR) task with graded levels of difficulty, based upon spatial displacement and a variable intertrial interval. Using this paradigm, microgram doses of nicotine produced a consistent reduction in the level of omissions and an improvement in proportion correct in normal mice. This improvement in sustained attention was made irrespectively of whether mice had previously received nicotine. In an attempt to elucidate which nicotinic acetylcholine receptor (nAChR) subtype(s) mediate this effect, we examined the performance of alpha7 nAChR knockout (KO) mice in the 5-CSR task. alpha7 nAChR KO mice not only acquired the task more slowly than their wild-type littermates, but on attaining asymptotic performance, they exhibited a higher level of omissions. In conclusion, by increasing the level of task difficulty, the performance of mice was maintained at sufficiently low levels to allow a demonstrable improvement in performance upon nicotine administration. Furthermore, as alpha7 KO mice are clearly impaired in the acquisition and asymptotic performance of this task, the alpha7 nAChR may be involved in mediating these effects of nicotine.
在人类中，尼古丁已被证明能改善正常人和受损个体的注意力。对大鼠的观察反映了尼古丁对人类注意力改善作用的一些方面，但并非全部。迄今为止，这些发现尚未在小鼠中得到重复验证。为了研究尼古丁对小鼠持续注意力的影响，我们基于空间位移和可变的试验间隔时间，建立了一个具有不同难度等级的五选择连续反应时（5-CSR）任务版本。使用这个范式，微克剂量的尼古丁使正常小鼠的遗漏水平持续降低，正确比例提高。这种持续注意力的改善与小鼠之前是否接受过尼古丁无关。为了阐明哪种烟碱型乙酰胆碱受体（nAChR）亚型介导了这种效应，我们检测了α7 nAChR基因敲除（KO）小鼠在5-CSR任务中的表现。α7 nAChR KO小鼠不仅比它们的野生型同窝小鼠学习任务的速度更慢，而且在达到渐近表现时，它们表现出更高的遗漏水平。总之，通过增加任务难度水平，小鼠的表现被维持在足够低的水平，以便在给予尼古丁后能明显改善表现。此外，由于α7 KO小鼠在这项任务的学习和渐近表现中明显受损，α7 nAChR可能参与介导尼古丁的这些效应。
