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D1样和D2样多巴胺受体在大鼠齿状回中对吗啡诱导的条件性位置偏爱形成、表达及消退的影响

Involvement of D1- and D2-like dopamine receptors in the dentate gyrus in the acquisition, expression, and extinction of the morphine-induced conditioned place preference in rats.

作者信息

Katebi Najmeh, Farahimanesh Sharareh, Fatahi Zahra, Zarrabian Shahram, Haghparast Abbas

机构信息

Neuroscience Research Center, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Institute for Cognitive Science Studies (ICSS), Tehran, Iran.

出版信息

Behav Brain Res. 2018 Nov 1;353:185-193. doi: 10.1016/j.bbr.2018.07.018. Epub 2018 Jul 24.

Abstract

In the current study, we investigated the role of intra-dentate gyrus (DG) administration of D1 and/or D2 receptor antagonists on the expression, acquisition, and extinction of morphine-CPP. Cannulae were implanted bilaterally into the DG region in male Wistar rats and CPP was induced by the subcutaneous injection of morphine (5 mg/kg) during a 3-day conditioning phase. Three experimental designs were separately employed in the CPP paradigm during the acquisition, expression and extinction phases, and different doses (0.25, 1, or 4 μg/0.5 μl saline) of SCH23390, as a selective D1-like receptor antagonist, and sulpiride (0.25, 1, or 4 μg/0.5 μl DMSO), as a selective D2-like receptor antagonist, were bilaterally microinjected into the DG region. Conditioning scores and locomotor activities were recorded during the test. Results showed that the injection of the antagonists into the DG region dose-dependently attenuated the acquisition and expression of the morphine-induced CPP and sulpiride revealed prominent behavioral results compared to SCH23390 in both mentioned phases. Moreover, the blockade of D1- and D2-like receptors shortened the extinction phase of the morphine-induced CPP but had no effect on the locomotor activity. We found that the dopamine receptors within the DG region are involved in the acquisition and expression of morphine-CPP and have a critical role in the association between a morphine-paired context and the rewarding proprieties of morphine.

摘要

在本研究中,我们探究了齿状回(DG)内注射D1和/或D2受体拮抗剂对吗啡条件性位置偏爱(CPP)的表达、获得及消退的作用。将套管双侧植入雄性Wistar大鼠的DG区,在为期3天的条件反射阶段通过皮下注射吗啡(5 mg/kg)诱导产生CPP。在CPP范式的获得、表达和消退阶段分别采用三种实验设计,将不同剂量(0.25、1或4 μg/0.5 μl生理盐水)的选择性D1样受体拮抗剂SCH23390和选择性D2样受体拮抗剂舒必利(0.25、1或4 μg/0.5 μl二甲基亚砜)双侧微量注射到DG区。在测试过程中记录条件反射分数和运动活动。结果显示,向DG区注射拮抗剂可剂量依赖性地减弱吗啡诱导的CPP的获得和表达,且在上述两个阶段中,与SCH23390相比,舒必利显示出更显著的行为学结果。此外,阻断D1和D2样受体可缩短吗啡诱导的CPP的消退期,但对运动活动无影响。我们发现,DG区内的多巴胺受体参与了吗啡CPP的获得和表达,并且在吗啡配对环境与吗啡奖赏特性之间的关联中起关键作用。

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