Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers.
Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers.
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DOI：
10.1016/j.bbi.2022.08.016
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发表时间：
2022-11
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影响因子：
--
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中科院分区：
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免疫-大脑相互作用影响成瘾的病理生理学。脂多糖（LPS）诱导的全身性炎症对奖励相关的脑区和多巴胺系统产生影响。我们先前表明，LPS放大哌甲酯（MP）诱导的多巴胺升高，与安慰剂（PBO）相比，在8名健康对照。然而，LPS对吸烟者多巴胺系统的影响尚未被探索。研究1的目的是在一个独立的吸烟者队列中复制先前的研究结果。研究2的目的是将联合收割机吸烟者与上述8名健康对照者相结合，以检查LPS对异质样本中多巴胺升高的影响，以确定功效和效应量。8名吸烟者分别在基线、LPS（0.8 ng/kg，静脉注射）和MP（40 mg，口服）给药后以及PBO和MP给药后，以双盲、随机顺序进行[11 C]雷氯必利正电子发射断层扫描3次。多巴胺升高定量为[11 C]雷氯必利结合潜力（ΔBPND）较基线的变化。进行重复测量ANOVA以比较LPS和PBO条件。吸烟者和健康对照组在人口统计学、药物剂量和扫描参数方面匹配良好。在研究1中，对于吸烟者，LPS后MP诱导的纹状体多巴胺升高显著高于PBO（p = 0.025，18 ± 2.9% vs 13 ± 2.7%）。在研究2中，在组合样品中，在LPS下MP诱导的纹状体多巴胺升高也显著高于在PBO下（p < 0.001，18 ± 1.6%对11 ± 1.5%）。吸烟状态与条件的影响没有相互作用。这是第一项将免疫系统实验激活后多巴胺升高放大的现象转化为成瘾样本的研究，这可能对药物强化，寻求和治疗产生影响。
Immune-brain interactions influence the pathophysiology of addiction. Lipopolysaccharide (LPS)-induced systemic inflammation produces effects on reward-related brain regions and the dopamine system. We previously showed that LPS amplifies dopamine elevation induced by methylphenidate (MP), compared to placebo (PBO), in eight healthy controls. However, the effects of LPS on the dopamine system of tobacco smokers have not been explored. The goal of Study 1 was to replicate previous findings in an independent cohort of tobacco smokers. The goal of Study 2 was to combine tobacco smokers with the aforementioned eight healthy controls to examine the effect of LPS on dopamine elevation in a heterogenous sample for power and effect size determination. Eight smokers were each scanned with [11C]raclopride positron emission tomography three times—at baseline, after administration of LPS (0.8 ng/kg, intravenously) and MP (40 mg, orally), and after administration of PBO and MP, in a double-blind, randomized order. Dopamine elevation was quantified as change in [11C]raclopride binding potential (ΔBPND) from baseline. A repeated-measures ANOVA was conducted to compare LPS and PBO conditions. Smokers and healthy controls were well-matched for demographics, drug dosing, and scanning parameters. In Study 1, MP-induced striatal dopamine elevation was significantly higher following LPS than PBO (p = 0.025, 18 ± 2.9 % vs 13 ± 2.7 %) for smokers. In Study 2, MP-induced striatal dopamine elevation was also significantly higher under LPS than under PBO (p < 0.001, 18 ± 1.6 % vs 11 ± 1.5 %) in the combined sample. Smoking status did not interact with the effect of condition. This is the first study to translate the phenomenon of amplified dopamine elevation after experimental activation of the immune system to an addicted sample which may have implications for drug reinforcement, seeking, and treatment.
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影响因子：
5.3
作者：
Felger JC
通讯作者：
Felger JC
影响因子：
4.7
作者：
Heinisch, Silke;Kirby, Lynn G.
通讯作者：
Kirby, Lynn G.
影响因子：
7.6
作者：
Brody, Arthur L.;Hubert, Robert;Mandelkern, Mark A.
通讯作者：
Mandelkern, Mark A.
影响因子：
4.8
作者：
Felger, Jennifer C.;Hernandez, Carla R.;Miller, Andrew H.
通讯作者：
Miller, Andrew H.
DOI：
10.1523/jneurosci.4284-11.2012
发表时间：
2012-05-23
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
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
通讯作者：
London ED