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首页> 外文期刊>Addiction biology >The relationship between naloxone-induced cortisol and delta opioid receptor availability in mesolimbic structures is disrupted in alcohol-dependent subjects
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The relationship between naloxone-induced cortisol and delta opioid receptor availability in mesolimbic structures is disrupted in alcohol-dependent subjects

机译：在酒精依赖性受试者中，纳洛酮诱导的皮质醇和中脑边缘结构中的阿片样物质受体三角洲之间的关系被破坏

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Hypothalamic-pituitary-adrenal (HPA) axis responses following naloxone administration have been assumed to provide a measure of opioid receptor activity. Employing positron emission tomography (PET) using the mu opioid receptor (MOR) selective ligand [11C] carfentanil (CFN), we demonstrated that cortisol responses to naloxone administration were negatively correlated with MOR availability. In this study, we examined whether naloxone-induced cortisol and adrenocorticotropin (ACTH) responses in 15 healthy control and 20 recently detoxified alcohol-dependent subjects correlated with delta opioid receptor (DOR) availability in 15 brain regions using the DOR-selective ligand [11C] methyl-naltrindole (MeNTL) and PET imaging. The day after the scan, cortisol responses to cumulative doses of naloxone were determined. Peak cortisol and ACTH levels and area under the cortisol and ACTH curve did not differ by group. There were negative relationships between cortisol area under curve to naloxone and [11C] MeNTL-binding potential (BPND) in the ventral striatum, anterior cingulate, fusiform cortices, temporal cortex, putamen and a trend in the hypothalamus of healthy control subjects. However, in alcohol-dependent subjects, cortisol responses did not correlate with [11C]MeNTL BPND in any brain region. Plasma ACTH levels did not correlate with [11C]MeNTL BPND in either group. The study demonstrates that naloxone provides information about individual differences in DOR availability in several mesolimbic structures. The data also show that the HPA axis is intimately connected with mesolimbic stress pathways through opioidergic neurotransmission in healthy subjects but this relationship is disrupted during early abstinence in alcohol-dependent subjects.
机译：假定纳洛酮给药后下丘脑-垂体-肾上腺（HPA）轴反应可提供阿片受体活性的量度。使用正电子发射断层扫描（PET）使用mu阿片受体（MOR）选择性配体[11C]芬太尼（CFN），我们证明皮质醇对纳洛酮给药的反应与MOR的利用率呈负相关。在这项研究中，我们使用DOR选择性配体[11C]检查了15位健康对照者和20位最近解毒的酒精依赖者中纳洛酮诱导的皮质醇和肾上腺皮质激素（ACTH）反应是否与15个脑区的δ阿片受体（DOR）可用性相关。 ]甲基纳曲酮（MeNTL）和PET成像。扫描的第二天，确定皮质醇对纳洛酮累积剂量的反应。各组的皮质醇峰值和ACTH水平以及皮质醇和ACTH曲线下面积均无差异。在健康对照者的腹侧纹状体，前扣带回，梭状皮层，颞叶皮层，壳核和下丘脑的趋势中，与纳洛酮对应的曲线下皮质醇面积与[11C] MeNTL结合潜能（BPND）呈负相关。但是，在酒精依赖的受试者中，皮质醇反应在任何脑区域均与[11C] MeNTL BPND不相关。两组血浆血浆ACTH水平均与[11C] MeNTL BPND不相关。这项研究表明，纳洛酮可提供有关几种中胚层结构中DOR可用性的个体差异的信息。数据还显示，在健康受试者中，HPA轴通过视皮膜上皮神经传递与中脑边缘应激途径紧密相连，但在酒精依赖受试者的早期戒酒过程中，这种关系被破坏。

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