de Bruin Natasja, Mahieu Michel, Patel Tarah, Willems Roland, Lesage Anne, Megens Anton
Johnson and Johnson, Pharmaceutical Research and Development (J and J PRD), CNS Discovery Research, Beerse, Belgium.
Behav Brain Res. 2006 Sep 15;172(1):122-34. doi: 10.1016/j.bbr.2006.05.002. Epub 2006 Jun 9.
Assessment of cognition and information processing in mice is an important tool in preclinical research that focuses on the development of cognitive enhancing drugs. Analysis of transgenic (TG) and knockout (KO) mice is usually performed on a F2 B6x 129 background. In the present study, we have compared performance of F2 B6x 129 hybrid mice (F2 mice) with that of the two parental inbred strains (C57Bl/6J and 129sv mice), and a wild-type (WT) strain (with a combined B6x 129 background) in three cognitive/information processing paradigms. It was found that the F2 mice outperformed either of the parental strains and provide a control sample with good baseline performance in the Morris water maze (MWM). Reliable deficits could be obtained in learning and memory in this paradigm following injections with scopolamine (0.16 mg/kg) in the F2 mice, which can potentially be used to test effects of reference and novel compounds in order to develop cognitive enhancing drugs. Furthermore, it was shown that the four genotypes showed normal latent inhibition (LI) using the conditioned taste aversion (CTA) paradigm and exhibited no differences in prepulse inhibition (PPI) levels. Following the setup of these procedures in mice, we are now able to compare the effects of gene knockout/mutations used for target validation with results in the present study as a frame of reference.
对小鼠认知和信息处理能力的评估是临床前研究中的一项重要工具，该研究聚焦于认知增强药物的开发。对转基因（TG）和基因敲除（KO）小鼠的分析通常在F2 B6x 129背景下进行。在本研究中，我们在三种认知/信息处理范式下，比较了F2 B6x 129杂交小鼠（F2小鼠）与两种亲代近交系（C57Bl/6J和129sv小鼠）以及一种野生型（WT）品系（具有合并的B6x 129背景）的表现。结果发现，F2小鼠的表现优于任何一种亲代品系，并在莫里斯水迷宫（MWM）中提供了具有良好基线表现的对照样本。在F2小鼠中注射东莨菪碱（0.16 mg/kg）后，在此范式下的学习和记忆方面可获得可靠的缺陷，这有可能用于测试参考化合物和新型化合物的效果，以开发认知增强药物。此外，研究表明，这四种基因型在条件性味觉厌恶（CTA）范式中表现出正常的潜伏抑制（LI），并且在预脉冲抑制（PPI）水平上没有差异。在小鼠中建立这些程序后，我们现在能够将用于靶点验证的基因敲除/突变的效果与本研究结果作为参考框架进行比较。
