Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens
Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens
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DOI：
10.1038/npp.2009.162
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发表时间：
2010-01-01
影响因子：
7.6
通讯作者：
Dalley, Jeffrey W.
中科院分区：
文献类型：
--
作者：
Besson, Morgane;Belin, David;Dalley, Jeffrey W.
先前的研究已经确定了丘脑核（NAcb）作为冲动行为个体间差异的重要脑区。这种变化与大鼠腹侧纹状体中多巴胺（DA）D2/3受体可用性降低有关，在持续视觉注意的5-选择系列反应时间（5-CSRT）测试中表现出自发高水平的冲动性。本研究探讨了多巴胺D2/3受体在NAcb核心（NAcbC）和NAcb壳（NAcbS）的参与冲动。我们研究了DA D2/3受体拮抗剂（萘法多曲胺）和DA D2/3部分激动剂（阿立哌唑）直接注入选择高（HI）和低（LI）冲动大鼠的NAcbC或NAcbS对5-CSRT任务的影响。当注入HI大鼠的NAcbS时，Nafadotride显著增加冲动水平，但当注入HI大鼠的NAcbC时，冲动水平降低。相比之下，NAcb内微量输注阿立哌唑不影响冲动。全身给予萘法多曲胺对冲动行为没有影响，但增加了遗漏和正确反应次数，而全身注射阿立哌唑减少了冲动和持续行为，并增加了遗漏和正确反应次数。这些发现表明，在NAcbS和NAcbC的DA D2/3受体的冲动行为的对手调制。这种不同的作用可能与临床行为控制障碍的病因和治疗有关，包括注意缺陷多动障碍和药物成瘾。Neuropsychopharmacology（2010）35，560-569; doi：10.1038/npp.2009.162; 2009年10月21日在线发表
Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intra-NAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction. Neuropsychopharmacology (2010) 35, 560-569; doi: 10.1038/npp.2009.162; published online 21 October 2009