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Inverse changes in raphe and cortical 5-HT1B receptor availability after acute tryptophan depletion in healthy human subjects.
SYNAPSE ( IF 1.6 ) Pub Date : 2020-04-23 , DOI: 10.1002/syn.22159 Stephen R Baldassarri 1 , Eunkyung Park 2, 3 , Sjoerd J Finnema 2 , Beata Planeta 2 , Nabeel Nabulsi 2 , Soheila Najafzadeh 2 , Jim Ropchan 2 , Yiyun Huang 2 , Jonas Hannestad 4 , Kathleen Maloney 4 , Zubin Bhagwagar 4 , Richard E Carson 2
SYNAPSE ( IF 1.6 ) Pub Date : 2020-04-23 , DOI: 10.1002/syn.22159 Stephen R Baldassarri 1 , Eunkyung Park 2, 3 , Sjoerd J Finnema 2 , Beata Planeta 2 , Nabeel Nabulsi 2 , Soheila Najafzadeh 2 , Jim Ropchan 2 , Yiyun Huang 2 , Jonas Hannestad 4 , Kathleen Maloney 4 , Zubin Bhagwagar 4 , Richard E Carson 2
Affiliation
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Serotonergic neurotransmission plays a key role in the pathophysiology and treatment of various neuropsychiatric diseases. The purpose of this study was to investigate changes in serotonergic neurotransmission after acute tryptophan depletion (ATD) using positron emission tomography (PET) with [11C]P943, a 5‐HT1B receptor radioligand previously shown to be sensitive to changes in 5‐HT. Five healthy subjects were scanned on a high resolution PET scanner twice on the same day, before and approximately 5 hours after ingesting capsules containing an amino acid mixture that lacks tryptophan. For each scan, emission data were acquired for 120 min after intravenous bolus injection of [11C]P943. Binding potential (BP ND) values were estimated from parametric images using the second version of the multilinear reference tissue model (MRTM2, t * = 20 min) with cerebellar grey matter used as a reference region. The change in [11C]P943 binding (ΔBP ND, %) was calculated as (BP ND,post − BP ND,pre)/(BP ND,pre) × 100, and correlation analysis was performed to measure linear associations of ΔBP ND between raphe and other regions of interest (ROIs). ΔBP ND ranged from −6% to 45% in the raphe, with positive values indicating reduced competition from 5‐HT. In cortical regions, ΔBP ND ranged from −28% to 7%. While these changes did not reach significance, there were significant negative correlations of ΔBP ND of the raphe with those of cerebral cortical regions and the thalamus (e.g., r = −.96, p = .011 for average cortex). These findings support the hypothesis that raphe serotonin is a critical modulator of cortical serotonin release via projecting neurons in healthy human subjects.
中文翻译：
健康人类受试者急性色氨酸耗竭后中缝和皮质 5-HT1B 受体可用性的反向变化。
血清素能神经传递在各种神经精神疾病的病理生理学和治疗中起着关键作用。本研究的目的是使用正电子发射断层扫描 (PET) 和 [ 11 C]P943研究急性色氨酸耗竭 (ATD) 后血清素能神经传递的变化，[ 11 C]P943 是一种 5-HT 1B受体放射性配体，以前显示对 5- H T。在同一天，在摄入含有缺乏色氨酸的氨基酸混合物的胶囊之前和大约 5 小时后，五名健康受试者在高分辨率 PET 扫描仪上进行了两次扫描。对于每次扫描，在静脉推注[ 11 C]P943后120 分钟内采集排放数据。结合电位（BP ND) 值是使用第二版多线性参考组织模型 (MRTM2, t * = 20 分钟)从参数图像估计的，其中小脑灰质用作参考区域。在改变[ 11 C] P943结合（Δ BP ND，％）计算为（BP ND，交 - BP ND，预）/（BP ND，预）×100，并进行相关性分析来测量的线性关联Δ 中缝和其他感兴趣区域 (ROI) 之间的BP ND。Δ BP ND在中缝中的范围为 -6% 至 45%，正值表明来自 5-HT 的竞争减少。在皮质区域，ΔBP ND范围从 -28% 到 7%。而这些变化并没有达到显着性，有Δ的显著负相关BP ND与大脑皮质区域和丘脑（例如，中缝的[R = -.96，p = 0.011对于平均皮质）。这些发现支持了这样的假设，即中缝血清素是通过投射健康人类受试者的神经元释放皮质血清素的关键调节剂。
更新日期：2020-04-23
中文翻译：
健康人类受试者急性色氨酸耗竭后中缝和皮质 5-HT1B 受体可用性的反向变化。
血清素能神经传递在各种神经精神疾病的病理生理学和治疗中起着关键作用。本研究的目的是使用正电子发射断层扫描 (PET) 和 [ 11 C]P943研究急性色氨酸耗竭 (ATD) 后血清素能神经传递的变化，[ 11 C]P943 是一种 5-HT 1B受体放射性配体，以前显示对 5- H T。在同一天，在摄入含有缺乏色氨酸的氨基酸混合物的胶囊之前和大约 5 小时后，五名健康受试者在高分辨率 PET 扫描仪上进行了两次扫描。对于每次扫描，在静脉推注[ 11 C]P943后120 分钟内采集排放数据。结合电位（BP ND) 值是使用第二版多线性参考组织模型 (MRTM2, t * = 20 分钟)从参数图像估计的，其中小脑灰质用作参考区域。在改变[ 11 C] P943结合（Δ BP ND，％）计算为（BP ND，交 - BP ND，预）/（BP ND，预）×100，并进行相关性分析来测量的线性关联Δ 中缝和其他感兴趣区域 (ROI) 之间的BP ND。Δ BP ND在中缝中的范围为 -6% 至 45%，正值表明来自 5-HT 的竞争减少。在皮质区域，ΔBP ND范围从 -28% 到 7%。而这些变化并没有达到显着性，有Δ的显著负相关BP ND与大脑皮质区域和丘脑（例如，中缝的[R = -.96，p = 0.011对于平均皮质）。这些发现支持了这样的假设，即中缝血清素是通过投射健康人类受试者的神经元释放皮质血清素的关键调节剂。
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