Department of Radiology and Biomedical Imaging, Yale University, New Haven, CT, USA.
Department of Psychiatry, Yale University, New Haven, CT, USA.
Neuropsychopharmacology. 2018 Dec;43(13):2539-2547. doi: 10.1038/s41386-018-0199-1. Epub 2018 Sep 6.
Opioid receptors are implicated in alcoholism, other addictions, withdrawal, and depression, and are considered potential pharmacological targets for treatment. Our goal in the present study was to compare the availability of kappa opioid receptors (KOR) between an alcohol-dependent cohort (AD) and a healthy control cohort (HC). Sixty-four participants-36 AD and 28 HC-underwent PET scans with [C]LY2795050, a selective kappa antagonist tracer. Partial-volume correction was applied to all PET data to correct for atrophy. Volume of distribution (V) of the tracer was estimated regionally as a measure of KOR availability. V values of AD versus HC were compared for 15 defined ROIs. Multivariate analysis showed a main effect of group on V across these 15 ROIs. Post hoc tests showed that AD had significantly lower V and thus a lower KOR availability than HC in amygdala and pallidum (corrected for multiple comparisons). Exploratory analysis of change in V with age was conducted; V was not found to vary significantly with age in any region. Our findings of lower V in AD versus HC in multiple regions are in contrast to findings in the mu and delta opioid receptor systems of higher V in AD versus HC. Although age-related decline in receptors has previously been observed in the mu opioid receptor system, we found that KOR availability does not change with age.
阿片受体与酒精中毒、其他成瘾、戒断和抑郁有关，被认为是治疗的潜在药理学靶点。本研究的目的是比较酒精依赖患者队列（AD）和健康对照组（HC）之间κ 型阿片受体（KOR）的可利用性。64 名参与者——36 名 AD 和 28 名 HC——接受了 [C]LY2795050 的 PET 扫描，这是一种选择性的 κ 拮抗剂示踪剂。对所有 PET 数据都应用了部分体积校正，以校正萎缩。将示踪剂的分布容积（V）作为 KOR 可利用性的衡量标准进行区域性估计。将 AD 与 HC 的 V 值进行比较，比较了 15 个定义明确的 ROI。多变量分析显示，这些 15 个 ROI 上的 V 存在组间的主要效应。事后检验显示，与 HC 相比，AD 的 V 值显著降低，因此 KOR 可利用性较低，杏仁核和苍白球（经多重比较校正）。对 V 随年龄的变化进行了探索性分析；在任何区域，V 都没有随年龄显著变化。我们发现 AD 中 V 低于 HC 的多个区域与 AD 中 V 高于 HC 的 μ 和 δ 型阿片受体系统的发现相反。尽管以前在 μ 型阿片受体系统中观察到与年龄相关的受体下降，但我们发现 KOR 可利用性不会随年龄而变化。
