Systemic inflammation enhances stimulant-induced striatal dopamine elevation.
Systemic inflammation enhances stimulant-induced striatal dopamine elevation.
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DOI：
10.1038/tp.2017.18
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发表时间：
2017-03-28
影响因子：
6.8
通讯作者：
Morris ED
中科院分区：
文献类型：
--
作者：
Petrulli JR;Kalish B;Nabulsi NB;Huang Y;Hannestad J;Morris ED
中脑边缘多巴胺（DA）系统的变化与一系列神经精神疾病有关，包括成瘾、抑郁症和精神分裂症。神经免疫系统的功能障碍通常与此类疾病同时存在，并影响大脑的类似区域。本研究的目的是使用正电子发射断层扫描和多巴胺 D2 拮抗剂示踪剂 11C-雷氯必利，探讨急性免疫激活对纹状体 DA 水平的影响。通过口服哌甲酯 (MP) 激发来调节 DA 传输，以可靠地引起 DA 升高。 MP 引起的 DA 浓度升高是通过基线扫描中 11C-雷氯必利结合电位的变化来估计的。在 MP 后扫描之前，受试者以交叉设计的方式接受了免疫激活剂脂多糖 (LPS) 或安慰剂 (PBO) 的预处理。通过测量血浆中肿瘤坏死因子α（TNFα）、白细胞介素（IL）-6和IL-8浓度来证实免疫激活。八名健康受试者各扫描四次，以确定在 LPS 和 PBO 治疗前条件下 MP 诱导的 DA 升高。与 PBO 预处理相比，LPS 预处理后 MP 诱导的纹状体 DA 升高显着更大（P<0.01）。八名受试者中有七名做出了类似的反应。在尾状核和壳核中观察到这种效应（P<0.02），但在腹侧纹状体中不存在。与 PBO 相比，当受试者接受 LPS 预处理时，MP 引起的 DA 升高显着更大。在全身炎症存在的情况下，兴奋剂诱导的 DA 信号放大可能对我们理解成瘾和其他 DA 功能障碍疾病具有重要意义。
Changes in the mesolimbic dopamine (DA) system are implicated in a range of neuropsychiatric conditions including addiction, depression and schizophrenia. Dysfunction of the neuroimmune system is often comorbid with such conditions and affects similar areas of the brain. The goal of this study was to use positron emission tomography with the dopamine D2 antagonist tracer, 11C-raclopride, to explore the effect of acute immune activation on striatal DA levels. DA transmission was modulated by an oral methylphenidate (MP) challenge in order to reliably elicit DA elevation. Elevation in DA concentration due to MP was estimated via change in 11C-raclopride binding potential from the baseline scan. Prior to the post-MP scan, subjects were pre-treated with either the immune activator lipopolysaccharide (LPS) or placebo (PBO) in a cross-over design. Immune activation was confirmed by measuring tumor necrosis factor alpha (TNFα), interleukin (IL)-6 and IL-8 concentration in plasma. Eight healthy subjects were scanned four times each to determine the MP-induced DA elevation under both LPS and PBO pre-treatment conditions. MP-induced DA elevation in the striatum was significantly greater (P<0.01) after LPS pre-treatment compared to PBO pre-treatment. Seven of eight subjects responded similarly. This effect was observed in the caudate and putamen (P<0.02), but was not present in ventral striatum. DA elevation induced by MP was significantly greater when subjects were pre-treated with LPS compared to PBO. The amplification of stimulant-induced DA signaling in the presence of systemic inflammation may have important implications for our understanding of addiction and other diseases of DA dysfunction.