Behavioral alterations in rats prenatally exposed to valproic acid: Animal model of autism
Behavioral alterations in rats prenatally exposed to valproic acid: Animal model of autism
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DOI：
10.1038/sj.npp.1300518
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发表时间：
2005-01-01
影响因子：
7.6
通讯作者：
Przewlocki, R
中科院分区：
文献类型：
--
作者：
Schneider, T;Przewlocki, R
自闭症是一种严重的行为障碍，其特征是社会交往中的普遍障碍，语言和非语言交流的缺陷，以及刻板重复的行为和兴趣模式。最近，通过在妊娠第12.5天（VPA大鼠）将大鼠胎儿暴露于丙戊酸（VPA），建立了一种新的自闭症啮齿动物模型。该模型与人类数据在解剖学、病理学和病因学方面具有惊人的相似性;然而，它尚未在行为学上得到表征。为了确定VPA大鼠是否存在自闭症中观察到的行为畸变，在一系列测试中对其行为进行了广泛评估。本实验的结果表明，VPA大鼠表现出：（1）对疼痛的敏感性较低，对非疼痛刺激的敏感性较高，（2）声前脉冲抑制减弱，（3）运动和重复/刻板样多动与较低的探索活动相结合，（4）社会行为数量减少，社会行为潜伏期增加。此外，VPA大鼠表现出成熟延迟，体重较低，运动发育延迟，协调的一系列反射的整合减弱，嗅觉系统介导的筑巢反应延迟，以及正常的负趋地性。有趣的是，本文中描述的所有行为畸变都出现在青春期之前，这可以将自闭症的VPA大鼠模型与其他神经发育障碍的动物模型，特别是精神分裂症的啮齿动物模型区分开来。我们的研究结果进一步支持了所提出的VPA自闭症动物模型的有效性，这表明在VPA大鼠中观察到的行为改变模式与自闭症患者的行为障碍特征之间存在相似性。
Autism is a severe behavioral disorder characterized by pervasive impairments in social interactions, deficits in verbal and nonverbal communication, and stereotyped, repetitive patterns of behaviors and interests. Recently, a new rodent model of autism was created by exposure of rat fetuses to valproic acid (VPA) on the 12.5th day of gestation (VPA rats). The model has striking anatomical, pathological, and etiological similarities to human data; however, it has not been characterized behaviorally. In order to determine if VPA rats present behavioral aberrations observed in autism, their behavior was extensively evaluated in a battery of tests. The results of the present experiments demonstrate that VPA rats exhibit: (1) lower sensitivity to pain and higher sensitivity to nonpainful stimuli, (2) diminished acoustic prepulse inhibition, (3) locomotor and repetitive/stereotypic-like hyperactivity combined with lower exploratory activity, and (4) decreased number of social behaviors and increased latency to social behaviors. In addition, VPA rats showed delayed maturation, lower body weight, delayed motor development, and attenuated integration of a coordinated series of reflexes, delayed nest-seeking response mediated by olfactory system, and normal negative geotaxis. Interestingly, all behavioral aberrations described in this paper appear before puberty, which could distinguish the VPA rat model of autism from other animal models of neurodevelopmental disorders, especially rodent models of schizophrenia. Our results bring further support to validity of the proposed VPA animal model of autism, suggesting similarities between the observed pattern of behavioral alterations in VPA rats and features of disturbed behavior in autistic patients.