Gastambide Francois, Taylor Amy M, Palmer Clare, Svard Heta, Karjalainen Maija, Janhunen Sanna K, Tricklebank Mark, Bannerman David M
Lilly Centre for Cognitive Neuroscience, Eli Lilly & Co. Ltd, Erl Wood Manor, Windlesham, UK.
Department of Experimental Psychology, University of Oxford, Oxford, UK.
Psychopharmacology (Berl). 2015 Nov;232(21-22):4099-112. doi: 10.1007/s00213-014-3862-1. Epub 2015 Jan 31.
Adult rats exposed to methylazoxymethanol acetate (MAM) at embryonic day 17 (E17) display robust pathological alterations in the hippocampus. However, discrepancies exist in the literature regarding the behavioural effects of this pre-natal manipulation. Therefore, a systematic assessment of MAM E17-induced behavioural alterations was conducted using a battery of dorsal and ventral hippocampus-dependent tests. Compared to saline controls, MAM E17-treated rats displayed deficits in spatial reference memory in both the aversive hidden platform watermaze task and an appetitive Y-maze task. Deficits in the spatial reference memory watermaze task were replicated across three different cohorts and two laboratories. In contrast, there was little, or no, effect on the non-spatial, visible platform watermaze task or an appetitive, non-spatial, visual discrimination task, respectively. MAM rats were also impaired in the spatial novelty preference task which assesses short-term memory, and displayed reduced anxiety levels in the elevated plus maze task. Thus, MAM E17 administration resulted in abnormal spatial information processing and reduced anxiety in a number of hippocampus-dependent behavioural tests, paralleling the effects of dorsal and ventral hippocampal lesions, respectively. These findings corroborate recent pathological and physiological studies, further highlighting the usefulness of MAM E17 as a model of hippocampal dysfunction in at least some aspects of schizophrenia.
在胚胎第17天（E17）暴露于乙酸甲基偶氮甲醇（MAM）的成年大鼠海马体中表现出明显的病理改变。然而，关于这种产前操作的行为影响，文献中存在差异。因此，使用一系列依赖背侧和腹侧海马体的测试对MAM E17诱导的行为改变进行了系统评估。与生理盐水对照组相比，接受MAM E17处理的大鼠在厌恶隐藏平台水迷宫任务和奖赏性Y迷宫任务中的空间参考记忆均存在缺陷。空间参考记忆水迷宫任务中的缺陷在三个不同的队列和两个实验室中得到了重复验证。相比之下，对非空间的可见平台水迷宫任务或奖赏性非空间视觉辨别任务分别几乎没有影响或没有影响。MAM处理的大鼠在评估短期记忆的空间新奇偏好任务中也受损，并且在高架十字迷宫任务中表现出焦虑水平降低。因此，给予MAM E17会导致在一些依赖海马体的行为测试中出现异常的空间信息处理和焦虑减轻，分别与背侧和腹侧海马体损伤的影响相似。这些发现证实了最近的病理和生理研究，进一步突出了MAM E17作为精神分裂症至少某些方面海马体功能障碍模型的有用性。
