Institute of Physiology, Medical School, Pécs University, Pécs, Hungary; Centre for Neuroscience, Pécs University, Pécs, Hungary.
Institute of Physiology, Medical School, Pécs University, Pécs, Hungary; Molecular Neuroendocrinology and Neurophysiology Research Group, Szentágothai Research Centre, Pécs University, Pécs, Hungary; Centre for Neuroscience, Pécs University, Pécs, Hungary.
Behav Brain Res. 2020 Feb 3;379:112345. doi: 10.1016/j.bbr.2019.112345. Epub 2019 Nov 5.
Cognitive disturbances are among the most important features of schizophrenia, and have a significant role in the outcome of the disease. However, the treatment of cognitive symptoms is poorly effective. In order to develop new therapeutic opportunities, the MAM-E17 rat model of schizophrenia can be an appropriate implement. In the present study we investigated several cognitive capabilities of MAM-treated rats using radial arm maze (RAM) task, which corresponds to the recent research directives. Because of the diachronic appearance of schizophrenia symptoms and the early appearance of cognitive deficiencies, we carried out our experiments in three different age-periods of rats, i.e. in prepuberty, late puberty and adulthood. The performance of MAM-E17 rats was similar to control rats in the acquisition phase of RAM task, except for puberty. However, after rearrangement of reward positions (in the reverse paradigm) the number of errors of MAM-treated rats was higher in each age-period. In the reverse paradigm MAM-treated groups visited more frequently those non-rewarding arms, which were previously rewarding. Our results suggest that working memory of MAM-E17 rats is impaired. This deficit depends on the difficulty of the task and on the age-period. MAM-E17 rats seem to be more sensitive in puberty in comparison to controls. Diminished behavioral flexibility was shown as well. These behavioral results observed in MAM-E17 rats were similar to those of cognitive deficiencies in schizophrenia patients. Therefore, MAM-E17 model can be a useful implement for further research aiming to improve cognition in schizophrenia.
认知障碍是精神分裂症最重要的特征之一，对疾病的结果有重大影响。然而，认知症状的治疗效果不佳。为了开发新的治疗机会，可以使用 MAM-E17 精神分裂症大鼠模型作为适当的工具。在本研究中，我们使用放射臂迷宫 (RAM) 任务研究了 MAM 处理大鼠的几种认知能力，这与最近的研究方向相对应。由于精神分裂症症状的出现具有时间上的差异，且认知缺陷出现较早，我们在大鼠的三个不同年龄阶段进行了实验，即青春期前、青春期后期和成年期。MAM-E17 大鼠的表现与 RAM 任务的获得阶段的对照大鼠相似，除了青春期。然而，在奖励位置重新排列（反向范式）后，MAM 处理组的大鼠在每个年龄阶段的错误数都更高。在反向范式中，MAM 处理组更频繁地访问那些以前是奖励的非奖励臂。我们的结果表明，MAM-E17 大鼠的工作记忆受损。这种缺陷取决于任务的难度和年龄阶段。与对照组相比，MAM-E17 大鼠在青春期更敏感。行为灵活性也降低了。在 MAM-E17 大鼠中观察到的这些行为结果与精神分裂症患者的认知缺陷相似。因此，MAM-E17 模型可以作为进一步研究改善精神分裂症认知的有用工具。
