Beyer Dominik K E, Horn Lisa, Klinker Nadine, Freund Nadja
Division of Experimental and Molecular Psychiatry, Department of Psychiatry, Psychotherapy and Preventive Medicine, LWL University Hospital, Ruhr-University, 44801 Bochum, Germany.
Transl Neurosci. 2021 Nov 3;12(1):432-443. doi: 10.1515/tnsci-2020-0187. eCollection 2021 Jan 1.
The prefrontal dopamine D1 receptor (D1R) is involved in cognitive processes. Viral overexpression of this receptor in rats further increases the reward-related behaviors and even its termination induces anhedonia and helplessness. In this study, we investigated the risky decision-making during D1R overexpression and its termination. Rats conducted the rodent version of the Iowa gambling task daily. In addition, the methyl CpG-binding protein-2 (MeCP2), one regulator connecting the dopaminergic system, cognitive processes, and mood-related behavior, was investigated after completion of the behavioral tasks. D1R overexpressing subjects exhibited maladaptive risky decision-making and risky decisions returned to control levels following termination of D1R overexpression; however, after termination, animals earned less reward compared to control subjects. In this phase, MeCP2-positive cells were elevated in the right amygdala. Our results extend the previously reported behavioral changes in the D1R-manipulated animal model to increased risk-taking and revealed differential MeCP2 expression adding further evidence for a bipolar disorder-like phenotype of this model.
前额叶多巴胺 D1 受体（D1R）参与认知过程。在大鼠中通过病毒介导使该受体过度表达会进一步增加与奖赏相关的行为，甚至其表达终止会诱发快感缺失和无助感。在本研究中，我们调查了 D1R 过度表达及其终止过程中的风险决策。大鼠每天进行啮齿类动物版的爱荷华赌博任务。此外，在行为任务完成后，对连接多巴胺能系统、认知过程和情绪相关行为的一种调节因子——甲基 CpG 结合蛋白 2（MeCP2）进行了研究。D1R 过度表达的实验对象表现出适应不良的风险决策，在 D1R 过度表达终止后，风险决策恢复到对照水平；然而，在终止后，与对照实验对象相比，动物获得的奖赏更少。在此阶段，右侧杏仁核中 MeCP2 阳性细胞增多。我们的研究结果将先前报道的 D1R 操纵动物模型中的行为变化扩展至冒险行为增加，并揭示了 MeCP2 的差异表达，为该模型的双相情感障碍样表型提供了进一步的证据。
