Jin H-M, Shrestha Muna S, Bagalkot T R, Cui Y, Yadav B K, Chung Y-C
Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University, Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Republic of Korea.
Department of Neurology, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Neuroscience. 2015 Mar 12;288:167-77. doi: 10.1016/j.neuroscience.2014.12.043. Epub 2015 Jan 6.
The present study investigated the effects of chronic social defeat stress on several behavioral parameters, and the expression of dopaminergic markers, i.e., dopamine D1 receptors (D1Rs), dopamine D2 receptors (D2Rs), and dopamine and cyclic adenosine 3',5'-monophosphate-regulated phosphoprotein-32 (DARPP-32), in the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HIP) of mouse brains. After 10days of social defeat stress, the defeated mice were divided into two groups: one group underwent a series of behavioral tests. The other group was sacrificed on the 11th day and tissue samples were collected for Western blotting. The behavioral tests comprised tests of locomotion, light/dark preference, social interaction, as well as the novel object recognition test (NORT), Morris water maze, and forced swimming test (FST). We measured the expression of D1Rs, D2Rs, total DARPP-32, phospho-Thr34 or Thr75-DARPP-32 using Western blotting. The defeated mice showed increased anxiety- and depression-like behaviors, and impaired cognition. No significant differences in D1Rs and D2Rs expression were shown between defeated and control mice in any area studied. A significantly increased expression in total DARPP-32, and phospho-DARPP-32 was observed in the PFC or AMY of defeated mice. These data suggest that alterations in dopaminergic markers may be involved in anxiety- and depression-like behaviors, and cognitive impairment induced by social defeat stress.
本研究调查了慢性社会挫败应激对小鼠大脑前额叶皮质(PFC)、杏仁核(AMY)和海马体(HIP)中几种行为参数以及多巴胺能标志物(即多巴胺 D1 受体(D1Rs)、多巴胺 D2 受体(D2Rs)和多巴胺与环磷腺苷调节磷蛋白 32(DARPP - 32))表达的影响。在经历 10 天的社会挫败应激后,将受挫败的小鼠分为两组:一组进行一系列行为测试。另一组在第 11 天处死并收集组织样本用于蛋白质免疫印迹分析。行为测试包括运动能力测试、明暗偏好测试、社交互动测试以及新物体识别测试(NORT)、莫里斯水迷宫测试和强迫游泳测试(FST)。我们使用蛋白质免疫印迹法测量 D1Rs、D2Rs、总 DARPP - 32、磷酸化苏氨酸 34 或苏氨酸 75 - DARPP - 32 的表达。受挫败的小鼠表现出焦虑样和抑郁样行为增加以及认知受损。在任何研究区域中,受挫败小鼠与对照小鼠之间的 D1Rs 和 D2Rs 表达均未显示出显著差异。在受挫败小鼠的 PFC 或 AMY 中观察到总 DARPP - 32 和磷酸化 DARPP - 32 的表达显著增加。这些数据表明,多巴胺能标志物的改变可能与社会挫败应激诱导的焦虑样和抑郁样行为以及认知障碍有关。