Deficits in sensorimotor gating and tests of social behavior in a genetic model of reduced NMDA receptor function
Deficits in sensorimotor gating and tests of social behavior in a genetic model of reduced NMDA receptor function
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DOI：
10.1016/j.bbr.2004.01.008
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发表时间：
2004-08-31
影响因子：
2.7
通讯作者：
Koller, BH
中科院分区：
文献类型：
--
作者：
Duncan, GE;Moy, SS;Koller, BH
NMDA受体功能的降低被假设为精神分裂症的病理生理学的贡献。为了模拟慢性和发育性NMDA受体功能减退，开发了表达低水平NMDA受体的NMDA R1亚基（NR 1）的小鼠品系。本研究测试的假设，这些NR 1亚型小鼠会表现出缺陷的感觉和同种相互作用，类似于在精神分裂症患者中观察到的赤字。通过将来自C57 BL/6和129 Sv/Ev背景的杂合子小鼠（NR 1 +/-）杂交产生NR 1亚型突变纯合子（NR 1-/-）的F1杂交小鼠。为了评估感觉运动门控，在声惊吓的前脉冲抑制范例中测试小鼠。NR 1亚型小鼠表现出增加的声惊吓反应，也表现出赤字的前脉冲抑制。惊吓反应差异改变捕食者气味暴露在雄性NR 1-/-小鼠，与对照组小鼠相比。在社会关系测试中，野生型小鼠与NR 1-/-小鼠相比，花了更多的时间研究新小鼠。在居民入侵者测试中，发现野生型和突变小鼠之间的性别特异性攻击行为有明显的缺陷。这些数据支持的论点，NR 1亚型小鼠表现出改变感觉运动门控和典型的同种相互作用，让人想起与精神分裂症相关的行为障碍。NR 1亚型小鼠可以代表一个模型系统，以探索精神分裂症某些症状的新治疗和预防策略。(C)2004 Elsevier B. V.保留所有权利。
Reduced NMDA receptor function is hypothesized to contribute to the pathophysiology of schizophrenia. In order to model chronic and developmental NMDA receptor hypofunction, a mouse line was developed that expresses low levels of the NMDA R1 subunit (NR1) of the NMDA receptor. The present study tested the hypothesis that these NR1 hypomorphic mice would exhibit deficits in sensorimotor and conspecific interactions, analogous to deficits observed in schizophrenic patients. F1 hybrid mice homozygous for the NR1 hypomorphic mutation (NR1 -/-) were generated by crossing heterozygous mice (NR1 +/-) from C57BL/6 and 129 Sv/Ev backgrounds. To assess sensorimotor gating, mice were tested in the paradigm of prepulse inhibition of acoustic startle. The NR1 hypomorphic mice exhibited increased acoustic startle responses and also showed deficits in prepulse inhibition. Startle responses were differentially altered by predator odor exposure in the male NR1 -/- mice, in comparison to control mice. In a test of social affiliation, the wild type mice spent significantly more time investigating a novel mouse in comparison to the NR1 -/- mice. In a resident-intruder test, marked deficits were found in sex-specific aggressive behavior between the wild type and mutant mice. These data support the contention that the NR1 hypomorphic mice exhibit alterations in sensorimotor gating and typical conspecific interactions, reminiscent of behavioral disturbances associated with schizophrenia. The NR1 hypomorphic mice could represent a model system to explore novel treatment and preventative strategies for certain symptoms of schizophrenia. (C) 2004 Elsevier B.V. All rights reserved.