Department of Radiology, University of Pittsburgh, Pittsburgh, PA.
School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
Biol Psychiatry. 2020 Mar 15;87(6):570-576. doi: 10.1016/j.biopsych.2019.09.013. Epub 2019 Sep 25.
An imbalance between neuropeptides that promote stress and resilience, such as corticotropin-releasing factor and nociceptin, has been postulated to underlie relapse in addiction. The objective of this study was to develop a paradigm to image the in vivo interaction between stress-promoting neuropeptides and nociceptin (NOP) receptors in humans.
[C]NOP-1A positron emission tomography was used to measure the binding to NOP receptors at baseline (BASE) and following an intravenous hydrocortisone challenge (CORT) in 19 healthy control subjects. Hydrocortisone was used as a challenge because in microdialysis studies it has been shown to increase corticotropin-releasing factor release in extrahypothalamic brain regions such as the amygdala. [C]NOP-1A total distribution volume (V) in 11 regions of interest were measured using a 2-tissue compartment kinetic analysis. The primary outcome measure was hydrocortisone-induced ΔV calculated as (V - V)/V.
Hydrocortisone led to an acute increase in plasma cortisol levels. Regional [C]NOP-1A V was on average 11% to 16% higher in the post-hydrocortisone condition compared with the baseline condition (linear mixed model, condition, p = .005; region, p < .001; condition × region, p < .001). Independent Student's t tests in all regions of interest were statistically significant and survived multiple comparison correction. Hydrocortisone-induced ΔV was significantly negatively correlated with baseline V in several regions of interest.
Hydrocortisone administration increases NOP receptor availability. Increased NOP in response to elevated cortisol might suggest a compensatory mechanism in the brain to counteract corticotropin-releasing factor and/or stress. The [C]NOP-1A and hydrocortisone imaging paradigm should allow for the examination of interactions between stress-promoting neuropeptides and NOP in addictive disorders.
促应激和抗压神经肽（如促肾上腺皮质激素释放因子和孤啡肽）之间的失衡被认为是成瘾复发的基础。本研究旨在开发一种范式，以在人类中成像促进应激的神经肽与孤啡肽（NOP）受体之间的体内相互作用。
19 名健康对照者在基线（BASE）和静脉注射氢化可的松挑战（CORT）后使用 [C]NOP-1A 正电子发射断层扫描（PET）测量 NOP 受体的结合情况。使用氢化可的松作为挑战药物，是因为在微透析研究中，它已被证明可以增加下丘脑外脑区（如杏仁核）中的促肾上腺皮质激素释放因子释放。使用 2 组织区室动力学分析测量 11 个感兴趣区的 [C]NOP-1A 总分布容积（V）。主要观察指标为（V-V）/V 计算的氢化可的松诱导的ΔV。
氢化可的松导致血浆皮质醇水平急性升高。与基线相比，后氢化可的松条件下的平均区域 [C]NOP-1A V 高 11%至 16%（线性混合模型，条件，p=0.005；区域，p<0.001；条件×区域，p<0.001）。所有感兴趣区的独立学生 t 检验均具有统计学意义，并通过多重比较校正得以存活。氢化可的松诱导的ΔV 与几个感兴趣区的基线 V 显著负相关。
氢化可的松给药增加了 NOP 受体的可用性。皮质醇升高时 NOP 的增加可能表明大脑中存在一种补偿机制，以抵消促肾上腺皮质激素释放因子和/或应激。[C]NOP-1A 和氢化可的松成像范式应允许检查促进应激的神经肽与成瘾障碍中 NOP 之间的相互作用。
