Long-term evaluation of isolation-rearing induced prepulse inhibition deficits in rats: an update

Long-term evaluation of isolation-rearing induced prepulse inhibition deficits in rats: an update
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DOI:
10.1007/s00213-004-2139-5
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发表时间:
2005-06-01
期刊:
影响因子:
3.4
通讯作者:
Jones, DNC
Jones, DNC
中科院分区:
医学3区
文献类型:
--
作者:
Cilia, J;Hatcher, PD;Jones, DNC

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基本原理:从断奶开始在社会隔离中饲养的大鼠表现出前脉冲抑制(PPI)缺陷,这被认为是精神分裂症和其他精神疾病中观察到的感觉运动门控缺陷的模型。我们以前曾报道过,10个队列的李斯特连帽大鼠在隔离饲养显示出强大的和可靠的PPI赤字。目的:我们的方法与其他人使用的方法不同(韦斯和Feldon in Psychopharmacology 156(2-3):305-326,2001),最明显的是与PND 20 -22相比,在产后第28天(PND)断奶的幼仔。自我们的首次报告以来,我们又研究了18个在PND 28断奶的队列和1个在PND 21断奶的队列。方法:在断奶时,将雄性Lister Hooded幼仔单独(分离株)或分组(n= 5)圈养(分组)。8周后,使用固定的刺激间间隔(ISI)条件(脉冲= 110 dB/50 ms;前脉冲(PP)=75-80 dB/30 ms; ISI=100 ms)研究隔离和分组大鼠的惊吓和PPI反应。结果:随后18个队列中有14个队列的分离株显示PPI缺陷,所有28个队列的总体成功率为86%。对于成功队列,分离株的PPI %范围为12 - 26%,分组的PPI %范围为26 - 47%,而对于失败队列,PPI %范围为16-30%(分离株)和19-35%(分组)。在随后的19个队列中,只有5个表现出惊吓高反应性,这与PPI反应无关。来自PND 21断奶队列的分离株未显示PPI显著不足,这表明至少在我们手中需要在PND 28断奶。结论:这里提供的数据加强了我们最初的发现,即隔离饲养Lister Hooded大鼠提供了一个可行的PPI受损的非药理学模型。
Rationale: Rats reared in social isolation from weaning show prepulse inhibition ( PPI) deficits which are thought to model the sensorimotor gating deficits seen in schizophrenia and other psychiatric disorders. We have previously reported that ten cohorts of Lister Hooded rats reared in isolation showed robust and reliable PPI deficits. Objective: Our methodology differed from those used by others (Weiss and Feldon in Psychopharmacology 156 (2-3): 305-326, 2001), most notably in the weaning of pups at postnatal day (PND) 28 compared with PND20-22. Since our initial report, we have studied 18 more cohorts weaned at PND28 and one cohort weaned at PND21. Method: At weaning, male Lister Hooded pups were singly ( isolates) or group (n= 5) housed ( grouped). Eight weeks later, startle and PPI responses of isolates and grouped rats were investigated using conditions of fixed inter-stimulus interval (ISI) (pulse= 110 dB/50 ms; prepulse (PP)=75-80 dB/30 ms; ISI=100 ms). Results: Isolates from 14 of the subsequent 18 cohorts demonstrated PPI deficits, giving an overall success rate of 86% for all 28 cohorts. %PPI ranged from 12 to 26% in the isolates and from 26 to 47% in the grouped for the successful cohorts, compared to 16-30% (isolates) and 19-35% ( grouped) for those that failed. Only five out of the 19 subsequent cohorts demonstrated startle hyperreactivity, which was unrelated to PPI response. The isolates from the cohort weaned at PND21 did not show a significant deficit in PPI, suggesting, in our hands at least, a requirement for weaning at PND28. Conclusion: The data presented here reinforce our original findings that isolation-rearing of Lister Hooded rats provides a viable, non-pharmacological model of impaired PPI.