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腹侧苍白球中 D 多巴胺受体的激活对正常和精神分裂症模型(Wisket 大鼠)的感觉门控和食物动机学习的影响。

Effects of D dopamine receptor activation in the ventral pallidum on sensory gating and food-motivated learning in control and schizophrenia model (Wisket) rats.

机构信息

Institute of Physiology, Faculty of Medicine, University of Pécs, Pécs, Hungary; Centre for Neuroscience, Pécs University, Pécs, Hungary.

Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.

出版信息

Behav Brain Res. 2021 Feb 26;400:113047. doi: 10.1016/j.bbr.2020.113047. Epub 2020 Dec 3.

DOI:10.1016/j.bbr.2020.113047
PMID:33279633
Abstract

Dopamine D receptors (DRs) of the ventral pallidum (VP) play important role in motivational and learning processes, however, their potential role in triggering schizophrenic symptoms has not been investigated, yet. In the present experiments the effects of locally administered DR agonist quinpirole were investigated on behavioral parameters related to sensorimotor gating, motor activity and food-motivated labyrinth learning. Two weeks after bilateral implantation of microcannulae into the VP, the acute (30 min) and delayed (3, 21 and 24 h) effects of quinpirole microinjection (1 μg/0.4 μL at both sides) were investigated in Wistar and schizophrenia model (Wisket substrain) rats in prepulse inhibition (PPI) and the reward-based Ambitus tests. Quinpirole administration did not modify the impaired sensorimotor gating in Wisket rats, but it led to significant deficit in Wistar animals. Regarding the locomotor activity in the Ambitus test, no effects of quinpirole were detected in either groups at the investigated time points. In contrast, quinpirole resulted in decreased exploratory and food-collecting activities in Wistar rats with 21 and 24 h delay. Though, impaired food-related motivation could be observed in Wisket rats, but quinpirole treatment did not result in further deterioration. In summary, our results showed that the VP DR activation in Wistar rats induces symptoms similar to those observed in schizophrenia model Wisket rats. These data suggest that Wisket rats might have significant alterations in the functional activity of VP, which might be due to its enhanced dopaminergic activity.

摘要

腹侧苍白球(VP)中的多巴胺 D 受体(DRs)在动机和学习过程中发挥着重要作用,然而,它们在引发精神分裂症症状方面的潜在作用尚未得到研究。在本实验中,研究了局部给予 DR 激动剂喹吡罗对与感觉运动门控、运动活动和食物动机性迷路学习相关的行为参数的影响。在双侧 VP 植入微导管 2 周后,在 Wistar 和精神分裂症模型(Wisket 亚系)大鼠中研究了喹吡罗微注射(两侧各 1μg/0.4μL,急性 30 分钟和延迟 3、21 和 24 小时)对 prepulse inhibition(PPI)和奖励性 Ambitus 测试的影响。喹吡罗给药不会改变 Wisket 大鼠的感觉运动门控受损,但会导致 Wistar 动物出现明显缺陷。关于 Ambitus 测试中的运动活动,在研究的时间点,喹吡罗在两组中均未产生影响。相比之下,喹吡罗导致 Wistar 大鼠在 21 和 24 小时延迟时表现出探索和食物收集活动减少。然而,在 Wisket 大鼠中可以观察到与食物相关的动机受损,但喹吡罗治疗并没有导致进一步恶化。总之,我们的结果表明,Wistar 大鼠 VP 中的 DR 激活会引起类似于 Wisket 精神分裂症模型大鼠所观察到的症状。这些数据表明,Wisket 大鼠的 VP 功能活动可能发生了重大变化,这可能是由于其多巴胺能活性增强所致。

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