The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model.
The role of the dopamine D1 receptor in social cognition: studies using a novel genetic rat model.
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DOI：
10.1242/dmm.024752
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发表时间：
2016-10-01
影响因子：
4.3
通讯作者：
Ellenbroek BA
中科院分区：
文献类型：
--
作者：
Homberg JR;Olivier JD;VandenBroeke M;Youn J;Ellenbroek AK;Karel P;Shan L;van Boxtel R;Ooms S;Balemans M;Langedijk J;Muller M;Vriend G;Cools AR;Cuppen E;Ellenbroek BA
社会认知是精神分裂症和其他几种（共病）精神疾病中受损的内在表型。多巴胺是社会认知的调节剂之一，但它的作用尚不清楚。多巴胺的作用是通过多巴胺受体介导的，包括多巴胺D1受体（Drd1）。由于目前的Drd 1受体激动剂不是Drd 1选择性的，药理学工具不足以描述Drd 1的作用。在这里，我们描述了一种新的大鼠模型与基因突变的Drd1中，我们测量了基本的行为表型和社会认知。预测I116S突变使受体不太稳定。与这种计算预测一致，这种Drd1突变导致Drd1跨膜插入减少，而通过Drd1 mRNA水平测量的Drd1表达保持不受影响。由于跨膜Drd1插入减少，突变大鼠表现出正常的基本运动和神经参数，以及自发活动和焦虑样行为。然而，社会认知的措施，如社会互动，气味标记，幼鼠超声波发声和社交能力，在突变大鼠中大大减少。Drd 1突变大鼠的这种特征为神经科学领域提供了一种新的遗传大鼠模型，用于研究一系列精神疾病，包括精神分裂症，自闭症，抑郁症，双相情感障碍和药物成瘾。总结：具有新型多巴胺D1受体突变的大鼠，其导致膜Drd1表达减少，显示出受损的社会认知，尽管它们的探索和焦虑样行为不受影响。
Social cognition is an endophenotype that is impaired in schizophrenia and several other (comorbid) psychiatric disorders. One of the modulators of social cognition is dopamine, but its role is not clear. The effects of dopamine are mediated through dopamine receptors, including the dopamine D1 receptor (Drd1). Because current Drd1 receptor agonists are not Drd1 selective, pharmacological tools are not sufficient to delineate the role of the Drd1. Here, we describe a novel rat model with a genetic mutation in Drd1 in which we measured basic behavioural phenotypes and social cognition. The I116S mutation was predicted to render the receptor less stable. In line with this computational prediction, this Drd1 mutation led to a decreased transmembrane insertion of Drd1, whereas Drd1 expression, as measured by Drd1 mRNA levels, remained unaffected. Owing to decreased transmembrane Drd1 insertion, the mutant rats displayed normal basic motoric and neurological parameters, as well as locomotor activity and anxiety-like behaviour. However, measures of social cognition like social interaction, scent marking, pup ultrasonic vocalizations and sociability, were strongly reduced in the mutant rats. This profile of the Drd1 mutant rat offers the field of neuroscience a novel genetic rat model to study a series of psychiatric disorders including schizophrenia, autism, depression, bipolar disorder and drug addiction. Summary: Rats with a novel dopamine D1 receptor mutation, which causes reduced membrane Drd1 expression, display impaired social cognition, although their exploratory and anxiety-like behaviours are unaffected.
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影响因子：
7.6
作者：
ELLENBROEK, BA;WILLEMEN, APM;COOLS, AR
通讯作者：
COOLS, AR
影响因子：
4
作者：
BLUETPAJOT, MT;MOUNIER, F;KORDON, C
通讯作者：
KORDON, C
影响因子：
2.9
作者：
Krieger, E;Koraimann, G;Vriend, G
通讯作者：
Vriend, G
影响因子：
4.7
作者：
Campi KL;Greenberg GD;Kapoor A;Ziegler TE;Trainor BC
通讯作者：
Trainor BC
影响因子：
--
作者：
MARCONDES, F. K.;BIANCHI, F. J.;TANNO, A. P.
通讯作者：
TANNO, A. P.