The long-term effects of maternal deprivation depend on the genetic background
The long-term effects of maternal deprivation depend on the genetic background
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DOI：
10.1016/s0893-133x(00)00088-9
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发表时间：
2000-07-01
影响因子：
7.6
通讯作者：
Cools, AR
中科院分区：
文献类型：
--
作者：
Ellenbroek, BA;Cools, AR
精神分裂症的神经发育假说导致了一系列新的动物模型，其中早期操作的长期后果被调查。我们最近的研究表明，在Wistar大鼠中，24小时的母性剥夺（出生后）会增加阿波啡的敏感性，减少脉冲前抑制，这种现象也见于精神分裂症患者。在本文中，我们通过使用不同的下丘脑-垂体-肾上腺轴和多巴胺能敏感性不同的大鼠品系（Fischer 344和Lewis），研究了母性剥夺的影响是否依赖于特定的遗传背景。数据显示，Wistar大鼠的基础惊吓幅度不受母体剥夺的影响，但脉冲前抑制减弱，阿波啡敏感性增强。另一方面，Fischer 344大鼠的基础惊吓幅度和脉冲前抑制均未受到影响，但阿波啡敏感性降低。在Lewis大鼠中，母性剥夺显著降低了基础惊吓幅度，但不影响脉冲前抑制或阿吗啡敏感性。对母性剥夺的不同反应可以最好地解释为大鼠品系之间基线多巴胺敏感性的差异。由于在精神分裂症患者中也可以看到脉冲前抑制减少和对阿波啡的易感性增强，数据表明，母性剥夺的Wistar大鼠可能代表了精神分裂症（方面）的一个有趣的发育模型。[j] .中华医学会精神病学分会，2003。Elsevier Science Inc.出版。版权所有。
The neurodevelopmental hypothesis of schizophrenia has led to a series of new animal models in which the long term consequences of early manipulations are investigated. We have recently shown that a single 24-hr period of maternal deprivation (at postnatal day (pnd) 9) increases apomorphine susceptibility and decreases prepulse inhibition in Wistar rats, viz. phenomena also seen in schizophrenic patients. In the present paper, we investigated whether the effects of maternal deprivation were dependent on a specific genetic background, by using different rat strains (Fischer 344 and Lewis) that differ in the Hypothalamus-Pituitary-Adrenal axis and in dopaminergic sensitivity. The data show that in Wistar rats, basal startle amplitude was not affected by maternal deprivation, but prepulse inhibition was reduced, and apomorphine susceptibility enhanced. In Fischer 344 rats on the other hand, neither basal startle amplitude, nor prepulse inhibition were affected, but apomorphine susceptibility was reduced. In Lewis rats, maternal deprivation significantly reduced basal startle amplitude, but did not affect prepulse inhibition or apomorphine susceptibility. The differential response to maternal deprivation can best be explained by differences in baseline dopamine sensitivity between the rat strains. Since a reduced prepulse inhibition and an enhanced susceptibility to apomorphine is also seen in schizophrenic patients, the data indicate that maternally deprived Wistar rats may represent an interesting developmental model for (aspects of) schizophrenia. [Neuropsychopharmacology 23:99-106, 2000] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved.