Featherstone Robert E, Rizos Zoe, Nobrega José N, Kapur Shitij, Fletcher Paul J
Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Neuropsychopharmacology. 2007 Feb;32(2):483-92. doi: 10.1038/sj.npp.1301223. Epub 2006 Oct 11.
Gestational methylazoxymethanol acetate (MAM) exposure has been suggested to produce neural and behavioral abnormalities similar to those seen in schizophrenia. In order to assess MAM treatment as a model of schizophrenia, pregnant female rats were injected with MAM (22 mg/kg) on gestational day 17 and their offspring were assessed in adulthood on a series of cognitive tasks. The first experiment involved an attentional set-shifting task, a rodent analog of the Wisconsin card sort task. In experiment 2, animals were tested on the 5-choice serial reaction time task, a rodent analog of the continuous performance task. In the final experiment animals were assessed on a differential reinforcement of low rate of responding 20 s schedule of reinforcement (DRL-20), a task that is sensitive to changes in inhibitory control. In the first experiment, MAM-treated animals required a greater number of trials than controls to successfully learn an extradimensional shift on the set-shifting task, and had difficulties in learning to reverse a previously acquired discrimination. In contrast, MAM-treated animals showed little impairment on the 5-choice task, aside from a modest but consistent increase in premature responding. Finally, MAM exposed animals showed substantial impairments in DRL performance. Post-mortem analysis of brain tissue showed significant decreases in tissue weight in the hippocampus, parietal cortex, prefrontal cortex, and dorsal striatum of MAM-treated animals. These results support the notion that MAM treatment may simulate some aspects of schizophrenic cognition.
孕期暴露于乙酸甲基氧化偶氮甲醇（MAM）已被认为会产生与精神分裂症患者相似的神经和行为异常。为了评估MAM治疗作为精神分裂症模型的效果，在妊娠第17天给怀孕的雌性大鼠注射MAM（22毫克/千克），并在成年期对其后代进行一系列认知任务评估。第一个实验涉及注意力转换任务，这是威斯康星卡片分类任务的啮齿动物类似物。在实验2中，对动物进行5选串行反应时间任务测试，这是连续操作任务的啮齿动物类似物。在最后一个实验中，对动物进行低反应率强化20秒强化时间表（DRL - 20）的差异强化任务评估，该任务对抑制控制的变化敏感。在第一个实验中，接受MAM治疗的动物在成功学习集合转换任务中的维度外转换时比对照组需要更多的试验次数，并且在学习逆转先前获得的辨别方面存在困难。相比之下，接受MAM治疗的动物在5选任务上几乎没有受损，只是过早反应有适度但持续的增加。最后，暴露于MAM的动物在DRL表现上有明显受损。对脑组织的尸检分析显示，接受MAM治疗的动物海马体、顶叶皮质、前额叶皮质和背侧纹状体的组织重量显著下降。这些结果支持了MAM治疗可能模拟精神分裂症认知某些方面的观点。
