Cognitive effects of neonatal hippocampal lesions in a rat model of schizophrenia
Cognitive effects of neonatal hippocampal lesions in a rat model of schizophrenia
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DOI：
10.1016/s0893-133x(96)00132-7
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发表时间：
1996-12-01
影响因子：
7.6
通讯作者：
Levin, ED
中科院分区：
文献类型：
--
作者：
Chambers, RA;Moore, J;Levin, ED
损毁新生大鼠的腹侧海马区已被提出作为精神分裂症的实验模型。这种损伤会导致对苯丙胺的兴奋作用产生高反应性综合症，美容受损，社会互动中断，这些影响出现在青春期，很像精神分裂症。在目前的研究中，评估了新生儿腹侧海马区病变的持续性认知影响，因为海马区对于各种认知障碍至关重要，而且它是精神分裂症的重要特征。在放射臂迷宫中评估了空间学习和工作记忆，该迷宫对成人造成的海马区损伤的不良影响很敏感。受损的大鼠在整个训练过程中持续存在的放射臂迷宫选择准确率明显不足。无论是在青春期前还是在成年期，缺陷都会出现。尽管受损大鼠的运动能力很差，但它们对烟碱拮抗剂甲氨基甲胺和毒扁豆碱拮抗剂东莨菪碱的遗忘效应的敏感度明显降低。无论是受损组还是对照组，尼古丁或苯丙胺都没有明显的影响。新生儿腹侧海马区病变导致的空间学习和工作记忆的长期缺陷表明，与同龄的额叶皮质病变不同，海马区病变的影响在发育过程中无法克服。烟碱型和毒酪碱型乙酰胆碱(ACh)拮抗剂对遗忘性作用的抵抗表明，海马区是这些药物作用的关键部位。新生海马区病变可能为精神分裂症的认知障碍提供一个很好的模型，并可能有助于评估对抗精神分裂症认知障碍的新药物效果。(C)1996年美国神经精神药理学学院
Lesioning the ventral hippocampus of neonatal rats has been proposed as an experimental model of schizophrenia. This lesion causes a syndrome of hyperresponsivity to the stimulant effects of amphetamine, impaired grooming and disrupted social interactions, effects that emerge during adolescence, much like schizophrenia. Persisting cognitive effects of neonatal ventral hippocampal lesions were assessed in the current study, because the hippocampus is critically important for a variety of cognitive impairment and because it is an important feature a of schizophrenia. Spatial learning and working memory were assessed in the radial-arm maze, which is sensitive to the adverse effects of hippocampal lesions made in adults. Lesioned rats showed pronounced deficits in radial-arm maze choice accuracy that persisted throughout training. Deficits were seen during the prepubertal period as well as in adulthood. Even though the lesioned rats performed move poorly, they were significantly less sensitive to the amnestic effects of the nicotinic antagonist mecamylamine and the muscarinic antagonist scopolamine. No significant effects of nicotine or amphetamine were seen in either the lesioned or control groups. The long-lasting deficits in spatial learning and working memory resulting from neonatal ventral hippocampal lesions show that, unlike frontal cortical lesions during the same age, the effects of hippocampal lesions are not overcome during development. The resistance to the amnestic effects of nicotinic and muscarinic acetylcholine (ACh) antagonists suggests that the hippocampus is a critical site for the action of these drugs. Neonatal hippocampal lesions may provide a good model of the cognitive impairments of schizophrenia and may be useful to assess novel drug effects to counteract the cognitive deficits in schizophrenia. (C) 1996 American College of Neuropsychopharmacology