Striatal dopamine D₂/D₃ receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.
Striatal dopamine D₂/D₃ receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans.
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DOI：
10.1523/jneurosci.4284-11.2012
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发表时间：
2012-05-23
期刊：
影响因子：
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通讯作者：
London ED
中科院分区：
文献类型：
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作者：
Ghahremani DG;Lee B;Robertson CL;Tabibnia G;Morgan AT;De Shetler N;Brown AK;Monterosso JR;Aron AR;Mandelkern MA;Poldrack RA;London ED
冲动行为被认为反映了一种类似特质的特征，可以对个人的成功和幸福产生广泛的影响，但其神经生物学基础仍然难以捉摸。尽管纹状体多巴胺D2样受体与啮齿动物的冲动行为和行为抑制有关，但D2样受体在人类额纹状体回路中介导抑制控制的作用尚未显示。我们在一项健康研究参与者的研究中调查了这一作用，这些参与者接受了D2/D3多巴胺受体配体[18F]fallypride的正电子发射断层扫描，以及血氧水平依赖性功能磁共振成像（BOLD fMRI），同时进行了停止信号任务，一种反应抑制测试。纹状体多巴胺D2/D3受体的可用性与反应抑制的速度（停止信号反应时间）呈负相关，与额纹状体神经回路中抑制相关的fMRI激活呈正相关。涉及D2/D3受体可用性的相关性最强的背侧区域（尾状核和壳核）的纹状体，与多巴胺受体和反应抑制相关的动物研究结果一致。结果表明，人类纹状体D2样受体功能在介导行为控制的神经回路中起着重要作用，这种能力对于适应性反应至关重要，并且在各种常见的神经精神疾病中受到损害。
Impulsive behavior is thought to reflect a trait-like characteristic that can have broad consequences for an individual’s success and well-being, but its neurobiological basis remains elusive. Although striatal dopamine D2-like receptors have been linked with impulsive behavior and behavioral inhibition in rodents, a role for D2-like receptor function in frontostriatal circuits mediating inhibitory control in humans has not been shown. We investigated this role in a study of healthy research participants who underwent positron emission tomography with the D2/D3 dopamine-receptor ligand [18F]fallypride, and blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) while they performed the Stop-signal Task, a test of response inhibition. Striatal dopamine D2/D3-receptor availability was negatively correlated with speed of response inhibition (stop-signal reaction time), and positively correlated with inhibition-related fMRI activation in frontostriatal neural circuitry. Correlations involving D2/D3 receptor availability were strongest in the dorsal regions (caudate and putamen) of the striatum, consistent with findings of animal studies relating dopamine receptors and response inhibition. The results suggest that striatal D2-like receptor function in humans plays a major role in the neural circuitry that mediates behavioral control, an ability that is essential for adaptive responding and is compromised in a variety of common neuropsychiatric disorders.