Blondel A, Simon H, Sanger D J, Moser P
Synthélabo Recherche, Bagneux, France.
Behav Pharmacol. 1999 Nov;10(6-7):665-73. doi: 10.1097/00008877-199911000-00013.
Nicotine improves cognitive performance both in animals and in humans, particularly in tests involving attentional processes. The five-choice serial reaction time task (5-CSRTT) is widely used as a model of attentional performance in rats, and previous studies have demonstrated effects of nicotine in this task on measures such as improved reaction time. Using a modified version of this task (in which rats were required to respond to the disappearance of one of five stimulus lights), we evaluated the effects of repeated nicotine administration (0.3 mg/kg, intraperitoneally, on three occasions over 7 days) in drug-naive rats. After the first administration, nicotine increased accuracy and reduced inappropriate responding (anticipatory responses and responses during time-out) compared to performance following vehicle administration on the preceding day. However, with repeated administration the improvement in accuracy disappeared, and other effects became apparent. Thus, after the third administration the main effects of nicotine were to increase inappropriate responding and to reduce reaction times. A fourth administration 1-2 weeks later produced similar results to the third administration, suggesting that the effects of nicotine were now constant. Despite the general increase in inappropriate responding, there was no impairment in accuracy. In contrast to the response to repeated nicotine, the performance of the rats on the 3 vehicle days remained constant. These data demonstrate that the administration of nicotine to drug-naive subjects improves performance in the 5-CSRTT but that with repeated administration this effect disappears and is replaced by a profile in which inappropriate and impulsive responding predominate.
尼古丁可改善动物和人类的认知表现，尤其是在涉及注意力过程的测试中。五选择连续反应时任务（5-CSRTT）被广泛用作大鼠注意力表现的模型，先前的研究已经证明尼古丁在该任务中对诸如缩短反应时间等指标有影响。我们使用该任务的一个修改版本（要求大鼠对五个刺激光之一消失做出反应），评估了对未接触过药物的大鼠重复给予尼古丁（0.3mg/kg，腹腔注射，在7天内分三次）的效果。首次给药后，与前一天给予赋形剂后的表现相比，尼古丁提高了准确性并减少了不适当反应（预期反应和超时期间的反应）。然而，随着重复给药，准确性的提高消失了，其他效果变得明显。因此，第三次给药后，尼古丁的主要作用是增加不适当反应并缩短反应时间。1至2周后进行的第四次给药产生了与第三次给药相似的结果，表明尼古丁的效果现在是稳定的。尽管不适当反应总体上有所增加，但准确性并未受损。与对重复给予尼古丁的反应相反，大鼠在三天给予赋形剂期间的表现保持不变。这些数据表明，对未接触过药物的受试者给予尼古丁可改善其在5-CSRTT中的表现，但随着重复给药，这种效果消失，并被一种以不适当和冲动反应为主的表现所取代。
