BACKGROUND The neuropeptide transmitter nociceptin, which binds to the nociceptin/orphanin FQ peptide (NOP) receptor, is a core component of the brain's antistress system. Nociceptin exerts its antistress effect by counteracting the functions of corticotropin-releasing factor, the primary stress-mediating neuropeptide in the brain. Basic investigations support a role for medications that target nociceptin receptors in the treatment of alcohol use disorders. Thus, it is of high interest to measure the in vivo status of NOP receptors in individuals with alcohol use disorders. METHODS Here, we used [11C]NOP-1A and positron emission tomography to measure the in vivo binding to NOP receptors in 15 alcohol-dependent humans as identified by DSM-IV and 15 healthy control subjects matched for age, sex, and smoking status. Alcohol-dependent individuals with no comorbid psychiatric, medical, or drug abuse disorders were scanned following 2 weeks of outpatient monitored abstinence (confirmed with three times per week urine alcohol metabolite testing). [11C]NOP-1A distribution volume in regions of interest (including the amygdala, hippocampus, and midbrain, striatal, and prefrontal cortical subdivisions) was measured with kinetic analysis using the arterial input function. RESULTS Regional [11C]NOP-1A distribution volume in alcohol dependence was not significantly different compared with healthy control subjects. No relationship between [11C]NOP-1A distribution volume and other clinical measures (including duration and severity of alcohol abuse, craving, and anxiety or depressive symptoms) were significant after correction for the multiple hypotheses tested. CONCLUSIONS The results of this study do not support alterations in the binding to NOP receptors in alcohol dependence. However, this finding does not necessarily rule out alterations in nociceptin transmission in alcohol dependence.

中文翻译：

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酒精使用障碍中的伤害感受肽受体：使用 [ 11 C]NOP-1A 进行的正电子发射断层扫描研究


背景技术神经肽递质伤害感受肽（nociceptin）与伤害感受肽/孤啡肽FQ肽（NOP）受体结合，是大脑抗应激系统的核心成分。伤害感受肽通过抵消促肾上腺皮质激素释放因子（大脑中主要的应激介导神经肽）的功能来发挥其抗应激作用。基础研究支持针对伤害感受素受体的药物在治疗酒精使用障碍中的作用。因此，测量酒精使用障碍个体体内 NOP 受体的状态非常有意义。方法在这里，我们使用 [11C]NOP-1A 和正电子发射断层扫描来测量 DSM-IV 鉴定的 15 名酒精依赖者和 15 名年龄、性别和吸烟状况相匹配的健康对照受试者体内与 NOP 受体的结合。 。在门诊监测戒酒两周后，对没有共存精神、医学或药物滥用疾病的酒精依赖个体进行扫描（通过每周 3 次尿液酒精代谢物检测进行确认）。 [11C]NOP-1A 在感兴趣区域（包括杏仁核、海马、中脑、纹状体和前额皮质分区）的分布体积是通过使用动脉输入函数的动力学分析来测量的。结果 与健康对照受试者相比，酒精依赖的区域[11C]NOP-1A分布体积没有显着差异。在校正测试的多个假设后，[11C]NOP-1A 分布体积与其他临床指标（包括酗酒的持续时间和严重程度、渴望以及焦虑或抑郁症状）之间没有显着关系。结论 本研究的结果不支持酒精依赖中与 NOP 受体结合的改变。 然而，这一发现并不一定排除酒精依赖中伤害感受素传递的改变。