de Bruin N M W J, Fransen F, Duytschaever H, Grantham C, Megens A A H P
Johnson & Johnson Pharmaceutical Research and Development (J&J PRD), CNS Discovery Research, Belgium.
Physiol Behav. 2006 Dec 30;89(5):692-703. doi: 10.1016/j.physbeh.2006.08.009. Epub 2006 Sep 20.
Impaired attention is evident in several neurological and psychiatric disorders. In the present study, attentional capabilities were measured in the operant five-choice serial reaction time task (5-CSRTT) in male (C57BL/6Jx129Sv)F2 hybrid (B6129F2) mice. Main aims were to validate and standardize the test in these mice: to setup procedures, measure potential beneficial effects of sub-chronic nicotine in degraded versions of the 5-CSRTT (by decreasing stimulus duration, inducing white noise and making the stimuli unpredictable) and study disruptive effects of additional administration of the muscarinic antagonist scopolamine. During the baseline pre-nicotine sessions, the B6129F2 mice attained a very good performance in the test (95% accuracy). As stimulus duration was reduced from 2 s to 1 s, response accuracy of the mice decreased. Mice treated with nicotine (0.16 mg/kg) attained significantly higher response accuracy and had a lower percentage of incorrect responses in comparison with the solvent-treated animals. No further beneficial effects of nicotine were found. Reduced response accuracy was also obtained when stimulus duration was reduced from 1 s to 0.5 s and when a variable intertrial interval was introduced. Noise interpolation between trials did not impair performance. Finally, scopolamine (0.16 mg/kg) disrupted attentional functioning. Although most studies have been performed in rats, these results add to the existing evidence that the 5-CSRTT can also be used to assess attentional performance in mice. This offers the opportunity to test transgenic and knockout mice with similar background as the B6129F2 as animal models of psychiatric and neurological diseases.
注意力受损在多种神经和精神疾病中都很明显。在本研究中,通过操作性五选择连续反应时任务(5-CSRTT)对雄性(C57BL/6Jx129Sv)F2杂交(B6129F2)小鼠的注意力能力进行了测量。主要目的是在这些小鼠中验证和标准化该测试:制定程序,测量亚慢性尼古丁在5-CSRTT的退化版本中的潜在有益作用(通过缩短刺激持续时间、引入白噪声和使刺激不可预测),并研究额外给予毒蕈碱拮抗剂东莨菪碱的破坏作用。在尼古丁给药前的基线阶段,B6129F2小鼠在测试中表现非常出色(准确率95%)。随着刺激持续时间从2秒减少到1秒,小鼠的反应准确率下降。与溶剂处理的动物相比,用尼古丁(0.16毫克/千克)处理的小鼠获得了显著更高的反应准确率,且错误反应的百分比更低。未发现尼古丁有进一步的有益作用。当刺激持续时间从1秒减少到0.5秒以及引入可变的试验间隔时,反应准确率也降低了。试验间的噪声插入并未损害表现。最后,东莨菪碱(0.16毫克/千克)破坏了注意力功能。尽管大多数研究是在大鼠中进行的,但这些结果补充了现有证据,即5-CSRTT也可用于评估小鼠的注意力表现。这为将与B6129F2具有相似背景的转基因和基因敲除小鼠作为精神和神经疾病的动物模型进行测试提供了机会。