Chambers R A, Moore J, McEvoy J P, Levin E D
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Neuropsychopharmacology. 1996 Dec;15(6):587-94. doi: 10.1016/S0893-133X(96)00132-7.
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 functions and cognitive impairment and because it is an important feature 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 more 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.
损毁新生大鼠的腹侧海马体已被提议作为精神分裂症的一种实验模型。这种损伤会导致对苯丙胺的兴奋作用反应过度、梳理行为受损以及社交互动紊乱等症状，这些症状在青春期出现，与精神分裂症非常相似。在本研究中评估了新生大鼠腹侧海马体损伤的持续认知影响，因为海马体对于多种认知功能和认知障碍至关重要，并且它是精神分裂症的一个重要特征。在放射状臂迷宫中评估空间学习和工作记忆，该迷宫对成年期造成的海马体损伤的不利影响很敏感。损伤大鼠在放射状臂迷宫选择准确性方面表现出明显缺陷，且在整个训练过程中持续存在。在青春期前以及成年期都观察到了缺陷。尽管损伤大鼠表现更差，但它们对烟碱拮抗剂美加明和毒蕈碱拮抗剂东莨菪碱的遗忘作用明显不敏感。在损伤组或对照组中均未观察到尼古丁或苯丙胺的显著影响。新生大鼠腹侧海马体损伤导致的空间学习和工作记忆的长期缺陷表明，与同年龄段的额叶皮质损伤不同，海马体损伤的影响在发育过程中不会被克服。对烟碱和毒蕈碱型乙酰胆碱（ACh）拮抗剂遗忘作用的抗性表明海马体是这些药物作用的关键部位。新生海马体损伤可能为精神分裂症的认知障碍提供一个良好模型，并且可能有助于评估对抗精神分裂症认知缺陷的新型药物效果。
