Kállai Veronika, Tóth Attila, Gálosi Rita, Péczely László, Ollmann Tamás, Petykó Zoltán, László Kristóf, Kállai János, Szabó Imre, Karádi Zoltán, Lénárd László
Institute of Physiology, Medical School, Pécs University, Pécs, Hungary; Centre for Neuroscience, Pécs University, Pécs, Hungary.
Institute of Behavioral Sciences, Medical School, Pécs University, Pécs, Hungary; Centre for Neuroscience, Pécs University, Pécs, Hungary.
Behav Brain Res. 2017 Aug 14;332:75-83. doi: 10.1016/j.bbr.2017.05.065. Epub 2017 May 31.
The MAM-E17 model is one of the most accepted schizophrenia rat models, which follows the neurodevelopmental theory of the disease. While symptoms of MAM-E17 rats were studied extensively, their examinations were usually restricted to adulthood and in a few cases to prepuberty. It is well known, however, that schizophrenia symptoms often start at puberty or early adulthood. Therefore the purpose of this study was to investigate the behavioral characteristics of MAM-E17 rats in various tests throughout three different age-periods, namely in prepuberty, late puberty and adulthood. In open field test, MAM-E17 rats displayed increased locomotor activity, elevated sniffing frequency and, as tendency, enhanced rearing activity. The elevated activity turned up in late puberty and remained there in adulthood, too. There was also a deficient prepulse inhibition (PPI) of startle response in late puberty and adulthood, but not before puberty. In rotarod task, MAM-treated rats performed better than control rats. The enhanced performance on rotarod was only present in late puberty and adulthood. In elevated plus maze test MAM-treated rats displayed diminished anxiety mostly in prepuberty. Histological analysis revealed reduced volume and cell disarray in the dorsal hippocampus. This is the first comprehensive study about symptoms of MAM-E17 rats manifested in behavioral tests carried out in prepuberty, late puberty and adulthood. Results display the age-dependent appearance of schizophrenia symptoms in the same rats. The present findings provide basic information to accomplish the schizophrenia related animal research, as well as can also confer further data to develop preventive treatment for human patients.
MAM-E17模型是最被广泛接受的精神分裂症大鼠模型之一，它遵循该疾病的神经发育理论。虽然对MAM-E17大鼠的症状进行了广泛研究，但这些研究通常局限于成年期，少数情况下涉及青春期前。然而，众所周知，精神分裂症症状通常始于青春期或成年早期。因此，本研究的目的是调查MAM-E17大鼠在三个不同年龄阶段（即青春期前、青春期后期和成年期）的各种测试中的行为特征。在旷场试验中，MAM-E17大鼠表现出运动活动增加、嗅探频率升高，并且有增强的直立活动倾向。这种活动增强出现在青春期后期，并在成年期持续存在。在青春期后期和成年期，惊跳反应的前脉冲抑制（PPI）也存在缺陷，但在青春期前没有。在转棒试验中，MAM处理的大鼠比对照大鼠表现更好。转棒试验中的增强表现仅出现在青春期后期和成年期。在高架十字迷宫试验中，MAM处理的大鼠大多在青春期前表现出焦虑减轻。组织学分析显示背侧海马体积减小和细胞排列紊乱。这是第一项关于MAM-E17大鼠在青春期前、青春期后期和成年期进行的行为测试中表现出的症状的综合研究。结果显示了同一大鼠中精神分裂症症状的年龄依赖性出现。本研究结果为完成与精神分裂症相关的动物研究提供了基础信息，也可为开发人类患者的预防性治疗提供更多数据。
