RATIONALE Psychotic disorders, such as schizophrenia, as well as some mood disorders, such as bipolar disorder, have been suggested to share common biological risk factors. One such factor is reelin, a large extracellular matrix glycoprotein that regulates neuronal migration during development as well as numerous activity-dependent processes in the adult brain. The current study sought to evaluate whether a history of stress exposure interacts with endogenous reelin levels to modify behavioural endophenotypes of relevance to psychotic and mood disorders. METHODS Heterozygous Reeler Mice (HRM) and wildtype (WT) controls were treated with 50mg/L of corticosterone (CORT) in their drinking water from 6 to 9weeks of age, before undergoing behavioural testing in adulthood. We assessed methamphetamine-induced locomotor hyperactivity, prepulse inhibition (PPI) of acoustic startle, short-term spatial memory in the Y-maze, and depression-like behaviour in the Forced-Swim Test (FST). RESULTS HRM genotype or CORT treatment did not affect methamphetamine-induced locomotor hyperactivity, a model of psychosis-like behaviour. At baseline, HRM showed decreased PPI at the commonly used 100msec interstimulus interval (ISI), but not at the 30msec ISI or following challenge with apomorphine. A history of CORT exposure potentiated immobility in the FST amongst HRM, but not WT mice. In the Y-maze, chronic CORT treatment decreased novel arm preference amongst HRM, reflecting reduced short-term spatial memory. CONCLUSION These data confirm a significant role of endogenous reelin levels on stress-related behaviour, supporting a possible role in both bipolar disorder and schizophrenia. However, an interaction of reelin deficiency with dopaminergic regulation of psychosis-like behaviour remains unclear.

中文翻译：

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在强迫游泳测试中，reelin 和压力的相互作用，而不是多巴胺介导的运动过度活跃或前脉冲抑制中断：与精神病和情绪障碍的相关性

基本原理 精神障碍（例如精神分裂症）以及某些情绪障碍（例如双相情感障碍）被认为具有共同的生物学风险因素。一个这样的因素是 reelin，一种大的细胞外基质糖蛋白，在发育过程中调节神经元迁移以及成人大脑中的许多活动依赖过程。目前的研究试图评估压力暴露史是否与内源性 reelin 水平相互作用以改变与精神病和情绪障碍相关的行为内表型。方法 杂合 Reeler 小鼠 (HRM) 和野生型 (WT) 对照在 6 至 9 周龄的饮用水中用 50mg/L 的皮质酮 (CORT) 处理，然后在成年期进行行为测试。我们评估了甲基苯丙胺引起的运动过度活跃，声惊吓的前脉冲抑制 (PPI)、Y 迷宫中的短期空间记忆和强迫游泳测试 (FST) 中的抑郁样行为。结果 HRM 基因型或 CORT 治疗不影响甲基苯丙胺诱导的运动过度活跃，这是一种类似精神病的行为模型。在基线时，HRM 在常用的 100 毫秒刺激间隔 (ISI) 显示 PPI 降低，但在 30 毫秒 ISI 或阿扑吗啡激发后没有显示。CORT 暴露史增强了 HRM 而非 WT 小鼠 FST 中的不动性。在 Y 迷宫中，长期 CORT 治疗降低了 HRM 中新的手臂偏好，反映了短期空间记忆的减少。结论 这些数据证实了内源性 reelin 水平对压力相关行为的重要作用，支持双相情感障碍和精神分裂症的可能作用。然而，