Department of Forensic Science, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
Behav Brain Res. 2013 Apr 15;243:261-6. doi: 10.1016/j.bbr.2013.01.019. Epub 2013 Jan 25.
A central problem in understanding the dopamine system in anxiety and depression is to specify functions of different members of the dopamine receptor family. Recent studies have reported that the dopamine D2/D3 receptor agonist pramipexole exerts an antidepressant-like effect in the chronic mild stress model and in the behavioral despair model, suggesting dopamine D3 receptor may be an important target for antidepressant actions. The aim of the present study was to examine the role of dopamine D3 receptor on the anxiety-like and depression-like behaviors induced by immobilization stress. We subjected D3 receptor knockout (D3KO) mice to a series of behavioral paradigms after acute (1 h) or chronic (1 h a day for 14 days) immobilization stress. The results showed that immobilization stress significantly altered the anxiety-like behaviors (open field test and elevated plus maze) and depression-like behaviors (tail suspension test) in both D3KO mice and their wild-type littermates. Moreover, further analysis of the data indicated that the D3KO mice, but not their littermates, failed to show a change in immobility time in the tail suspension test after the acute and chronic stress as compared to intact controls, suggesting an increased resistance to the immobilization stress given before behavioral tests. Although our study did not suggest a significant role of D3 receptor in regulating basal anxiety-like and depression-like behaviors, it demonstrated the mice lacking D3 receptor might be more resistant to stressful procedure than their WT littermates.
理解焦虑和抑郁中的多巴胺系统的一个核心问题是明确多巴胺受体家族不同成员的功能。最近的研究报告表明,多巴胺 D2/D3 受体激动剂普拉克索在慢性轻度应激模型和行为绝望模型中表现出抗抑郁样作用,这表明多巴胺 D3 受体可能是抗抑郁作用的重要靶点。本研究的目的是研究多巴胺 D3 受体在束缚应激引起的焦虑样和抑郁样行为中的作用。我们在急性(1 小时)或慢性(每天 1 小时,持续 14 天)束缚应激后,使 D3 受体敲除(D3KO)小鼠经历一系列行为范式。结果表明,束缚应激显著改变了 D3KO 小鼠及其野生型同窝仔鼠的焦虑样行为(旷场试验和高架十字迷宫试验)和抑郁样行为(悬尾试验)。此外,进一步分析数据表明,与完整对照组相比,急性和慢性应激后,D3KO 小鼠而非其同窝仔鼠在悬尾试验中不能改变不动时间,表明在行为测试前给予束缚应激时,D3KO 小鼠的抵抗力增加。虽然我们的研究并未表明 D3 受体在调节基础焦虑样和抑郁样行为中具有重要作用,但它表明缺乏 D3 受体的小鼠可能比其 WT 同窝仔鼠更能抵抗应激程序。