BACKGROUND Schizophrenia (SCZ) is a neurodevelopmental disorder with a progressive, prolonged course. Early prevention for SCZ is promising but overall lacks support from preclinical evidence. Previous studies have tested environmental enrichment (EE) in certain models of SCZ and discovered a broadly beneficial effect in preventing behavioral abnormalities relevant, yet not specific, to the disorder. Nonetheless, whether EE can prevent dopamine (DA) dysregulation, a hallmark of psychosis and SCZ, had not been tested. METHODS Using the MAM (methylazoxymethanol acetate) rat model of schizophrenia and saline-treated control animals, we investigated the long-term electrophysiological effects of prepubertal (postnatal day 21-40) EE on DA neurons, pyramidal neurons in the ventral hippocampus, and projection neurons in the basolateral amygdala. Anxiety-related behaviors in the elevated plus maze and locomotor responses to amphetamine were also analyzed. RESULTS Prepubertal EE prevented the increased population activity of DA neurons and the associated increase in locomotor response to amphetamine. Prepubertal EE also prevented hyperactivity in the ventral hippocampus but did not prevent hyperactivity in the basolateral amygdala. Anxiety-like behaviors in MAM rats were not ameliorated by prepubertal exposure to EE. CONCLUSIONS Twenty-day prepubertal EE is sufficient to prevent DA hyperresponsivity in the MAM model, measured by electrophysiological recordings and locomotor response to amphetamine. This effect is potentially mediated by normalizing excessive firing in the ventral hippocampus without affecting anxiety-like behaviors and basolateral amygdala firing. This study identified EE as a useful preventative approach that may protect against the pathophysiological development of SCZ.

中文翻译：

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青春期前环境富集可防止 MAM 精神分裂症模型大鼠的多巴胺失调和海马过度活跃。

背景精神分裂症(SCZ)是一种具有进行性、延长病程的神经发育障碍。SCZ 的早期预防很有希望，但总体上缺乏临床前证据的支持。先前的研究已经在某些 SCZ 模型中测试了环境富集 (EE)，并发现在预防与该疾病相关但非特异性的行为异常方面具有广泛的有益作用。尽管如此，EE 是否可以预防多巴胺 (DA) 失调，这是精神病和 SCZ 的标志，尚未经过测试。方法 使用 MAM（甲基偶氮甲醇乙酸酯）大鼠精神分裂症模型和盐水处理的对照动物，我们研究了青春期前（出生后第 21-40 天）EE 对 DA 神经元、腹侧海马锥体神经元和投射的长期电生理影响基底外侧杏仁核中的神经元。还分析了高架十字迷宫中的焦虑相关行为和对安非他明的运动反应。结果青春期前 EE 阻止了 DA 神经元群体活动的增加以及对安非他明的运动反应的相关增加。青春期前 EE 还可以防止腹侧海马的过度活跃，但不能防止基底外侧杏仁核的过度活跃。MAM 大鼠的焦虑样行为并未因青春期前暴露于 EE 而得到改善。结论 20 天青春期前 EE 足以防止 MAM 模型中的 DA 高反应性，通过电生理记录和对安非他明的运动反应测量。这种效应可能通过使腹侧海马过度放电正常化而不影响焦虑样行为和基底外侧杏仁核放电来介导。