Bizarro L, Patel S, Murtagh C, Stolerman I P
Section of Behavioural Pharmacology, Institute of Psychiatry P049, King's College London, UK.
Behav Pharmacol. 2004 May;15(3):195-206.
Nicotine can improve attentional performance in the rat as assessed by a modified five-choice serial reaction time task (5-CSRTT), but it is not known if the effect is shared with other psychomotor stimulants. This study compared the effects of nicotine, amphetamine, caffeine and methylphenidate on performance in the 5-CSRTT and determined whether presenting stimuli at unpredictable times by using variable inter-trial intervals (ITI) influenced the sensitivity of the task to the drugs. One group of male hooded rats was trained to obtain food reinforcers by nose-poking in response to 1 s light stimuli presented randomly in one of five apertures, with fixed ITI; for a second group of rats, ITI varied randomly (n=12 per group). As observed previously, nicotine (tested in doses of 0.05-0.2 mg/kg) produced dose-related improvements in accuracy, reduced omission errors and response latencies, but increased anticipatory responding. Amphetamine (0.1-0.8 mg/kg) and methylphenidate (2.5-10 mg/kg) increased accuracy and reduced response latency, and decreased anticipatory responding. Caffeine (2.5-20 mg/kg) did not improve performance except at a small dose that decreased omission errors only. Training at different levels of stimulus predictability influenced performance in the undrugged state but had little impact on profiles of responses to the drugs. The findings with methylphenidate support the potential value of the 5-CSRTT for testing drugs that may be useful in the treatment of attention deficit hyperactivity disorder.
通过改良的五选择连续反应时任务(5-CSRTT)评估发现,尼古丁可改善大鼠的注意力表现,但尚不清楚这种作用是否与其他精神运动兴奋剂相同。本研究比较了尼古丁、苯丙胺、咖啡因和哌甲酯对5-CSRTT表现的影响,并确定通过使用可变的试验间隔(ITI)在不可预测的时间呈现刺激是否会影响该任务对药物的敏感性。一组雄性有帽大鼠接受训练,通过对随机出现在五个孔之一中的1秒光刺激进行鼻戳来获得食物强化,ITI固定;另一组大鼠的ITI随机变化(每组12只)。如先前观察到的,尼古丁(剂量为0.05 - 0.2mg/kg)在准确性方面产生了剂量相关的改善,减少了遗漏错误和反应潜伏期,但增加了预期反应。苯丙胺(0.1 - 0.8mg/kg)和哌甲酯(2.5 - 10mg/kg)提高了准确性,减少了反应潜伏期,并减少了预期反应。咖啡因(2.5 - 20mg/kg)除了在一个仅减少遗漏错误的小剂量时外,并未改善表现。在不同刺激可预测性水平下的训练影响了未用药状态下的表现,但对药物反应的特征影响很小。哌甲酯的研究结果支持了5-CSRTT在测试可能对治疗注意力缺陷多动障碍有用的药物方面的潜在价值。