Acute acetate administration increases endogenous opioid levels in the human brain: A [(11)C]carfentanil molecular imaging study.
Acute acetate administration increases endogenous opioid levels in the human brain: A [(11)C]carfentanil molecular imaging study.
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DOI：
10.1177/0269881120965912
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发表时间：
2021-05
期刊：
影响因子：
--
通讯作者：
Rabiner EA
中科院分区：
文献类型：
--
作者：
Ashok AH;Myers J;Frost G;Turton S;Gunn RN;Passchier J;Colasanti A;Marques TR;Nutt D;Lingford-Hughes A;Howes OD;Rabiner EA
最近的一项研究表明，醋酸盐的使用导致下丘脑中proopiomelanocortin (POMC) mRNA转录增加四倍。POMC被切割成多肽，包括β-内啡肽，一种内源性阿片（EO）激动剂，优先结合μ -阿片受体（MOR）。我们假设醋酸盐的挑战会增加人脑中EO的水平。我们之前已经证明，使用选择性MOR放射配体[11C]卡芬太尼的正电子发射断层扫描（PET）可以检测到人脑中EO释放的增加。我们使用这种方法来评估急性醋酸盐刺激对健康人类志愿者大脑中EO水平的影响。7名志愿者每人完成了一次基线卡芬太尼PET扫描，随后服用醋酸钠，然后进行第二次卡芬太尼PET扫描。在90分钟内获得动态PET数据，并对衰减、散射和主体运动进行校正。然后使用简化的参考组织模型（以枕部灰质为参考区域）计算区域[11C]卡芬太尼BPND值。用醋酸给药后[11C]卡芬太尼BPND的变化来评价区域EO浓度的变化。服用醋酸钠后，[11C]卡芬太尼区域BPND降低2.5-6.5%，在小脑、颞叶、眶额皮质、纹状体和丘脑中达到统计学意义。我们已经证明，急性醋酸盐刺激有可能增加人脑中EO的释放，这为醋酸盐对人类食欲的核心作用提供了一个合理的机制。
A recent study has shown that acetate administration leads to a fourfold increase in the transcription of proopiomelanocortin (POMC) mRNA in the hypothalamus. POMC is cleaved to peptides, including β-endorphin, an endogenous opioid (EO) agonist that binds preferentially to the µ-opioid receptor (MOR). We hypothesised that an acetate challenge would increase the levels of EO in the human brain. We have previously demonstrated that increased EO release in the human brain can be detected using positron emission tomography (PET) with the selective MOR radioligand [11C]carfentanil. We used this approach to evaluate the effects of an acute acetate challenge on EO levels in the brain of healthy human volunteers. Seven volunteers each completed a baseline [11C]carfentanil PET scan followed by an administration of sodium acetate before a second [11C]carfentanil PET scan. Dynamic PET data were acquired over 90 minutes, and corrected for attenuation, scatter and subject motion. Regional [11C] carfentanil BPND values were then calculated using the simplified reference tissue model (with the occipital grey matter as the reference region). Change in regional EO concentration was evaluated as the change in [11C]carfentanil BPND following acetate administration. Following sodium acetate administration, 2.5–6.5% reductions in [11C]carfentanil regional BPND were seen, with statistical significance reached in the cerebellum, temporal lobe, orbitofrontal cortex, striatum and thalamus. We have demonstrated that an acute acetate challenge has the potential to increase EO release in the human brain, providing a plausible mechanism of the central effects of acetate on appetite in humans.
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影响因子：
11
作者：
Pecina, M.;Zubieta, J-K
通讯作者：
Zubieta, J-K
影响因子：
25.8
作者：
Pecina, Marta;Bohnert, Amy S. B.;Zubieta, Jon-Kar
通讯作者：
Zubieta, Jon-Kar
影响因子：
5.7
作者：
Lammertsma, AA;Hume, SP
通讯作者：
Hume, SP
影响因子：
2.3
作者：
Joutsa, Juho;Karlsson, Henry K.;Nummenmaa, Lauri
通讯作者：
Nummenmaa, Lauri
影响因子：
5.7
作者：
Koepp, M. J.;Hammers, A.;Bench, C. J.
通讯作者：
Bench, C. J.