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Serotonin release measured in the human brain: a PET study with [11C]CIMBI-36 and d-amphetamine challenge.
Neuropsychopharmacology ( IF 7.6 ) Pub Date : 2019-11-12 , DOI: 10.1038/s41386-019-0567-5
David Erritzoe 1 , Abhishekh H Ashok 2, 3, 4 , Graham E Searle 5 , Alessandro Colasanti 6 , Samuel Turton 1 , Yvonne Lewis 5 , Mickael Huiban 5 , Sara Moz 5 , Jan Passchier 5 , Azeem Saleem 5 , John Beaver 5, 7 , Anne Lingford-Hughes 1 , David J Nutt 1 , Oliver D Howes 2, 3 , Roger N Gunn 1, 6 , Gitte M Knudsen 8 , Eugenii A Rabiner 6
Affiliation  

Positron emission tomography (PET) enables non-invasive estimation of neurotransmitter fluctuations in the living human brain. While these methods have been applied to dopamine and some other transmitters, estimation of 5-hydroxytryptamine (5-HT; Serotonin) release has proved to be challenging. Here we demonstrate the utility of the novel 5-HT2A receptor agonist radioligand, [11C]CIMBI-36, and a d-amphetamine challenge to evaluate synaptic 5-HT changes in the living human brain. Seventeen healthy male volunteers received [11C]CIMBI-36 PET scans before and 3 h after an oral dose of d-amphetamine (0.5 mg/kg). Dynamic PET data were acquired over 90 min, and the total volume of distribution (VT) in the frontal cortex and the cerebellum derived from a kinetic analysis using MA1. The frontal cortex binding potential (BPNDfrontal) was calculated as (VTfrontal/VTcerebellum) − 1. ∆BPNDfrontal = 1 − (BPNDfrontal post-dose/BPNDfrontal baseline) was used as an index of 5-HT release. Statistical inference was tested by means of a paired Students t-test evaluating a reduction in post-amphetamine [11C]CIMBI-36 BPNDfrontal. Following d-amphetamine administration, [11C]CIMBI-36 BPNDfrontal was reduced by 14 ± 13% (p = 0.002). Similar effects were observed in other cortical regions examined in an exploratory analysis. [11C]CIMBI-36 binding is sensitive to synaptic serotonin release in the human brain, and when combined with a d-amphetamine challenge, the evaluation of the human brain serotonin system in neuropsychiatric disorders, such as major depression and Parkinson’s disease is enabled.



中文翻译:

在人脑中测量的血清素释放:使用 [11C]CIMBI-36 和 d-苯丙胺挑战的 PET 研究。

正电子发射断层扫描 (PET) 能够对活的人脑中的神经递质波动进行非侵入性估计。虽然这些方法已应用于多巴胺和其他一些递质,但对 5-羟色胺(5-HT;5-羟色胺)释放的估计已被证明具有挑战性。在这里,我们展示了新型 5-HT2A 受体激动剂放射性配体 [ 11 C]CIMBI-36 和 d-苯丙胺挑战在评估活人大脑中突触 5-HT 变化的效用。17 名健康男性志愿者在口服 d-苯丙胺 (0.5 mg/kg) 之前和之后 3 小时接受了 [ 11 C]CIMBI-36 PET 扫描。动态 PET 数据在 90 分钟内采集,总分布容积 ( V T) 在额叶皮层和小脑中,来自使用 MA1 的动力学分析。额叶皮层结合电位 (BP ND frontal ) 计算为 ( V T frontal / V T cerebellum ) - 1. ΔBP ND frontal  = 1 - (BP ND frontal post-dose/BP ND frontal baseline) 用作指标5-HT 释放。统计推断通过配对学生t检验进行测试,评估后安非他明 [ 11 C]CIMBI-36 BP ND额叶的减少。服用 d-苯丙胺后,[ 11C]CIMBI-36 BP ND额叶减少 14 ± 13% ( p  = 0.002)。在探索性分析中检查的其他皮质区域也观察到了类似的效果。[ 11 C]CIMBI-36 结合对人脑中的突触血清素释放敏感,当与 d-苯丙胺激发结合时,可以评估人脑血清素系统在神经精神疾病(如重度抑郁症和帕金森病)中的作用.

更新日期:2019-11-13
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