Molecular Imaging Program, Clinical Neurosciences Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, Connecticut, USA.
Biol Psychiatry. 2010 May 1;67(9):800-3. doi: 10.1016/j.biopsych.2009.12.028. Epub 2010 Feb 20.
Although animal models suggest that alcohol dependence (AD) is associated with elevations in the number of serotonin 1B receptors (5-HT(1B)R), 5-HT(1B)R levels have not been investigated in people with AD. The selective 5-HT(1B)R antagonist radioligand, [(11)C]P943, permits in vivo assessment of central 5-HT(1B)R binding potential (BP(ND)) with positron emission tomography. Because of its central role in AD, we were particularly interested in ventral striatal 5-HT(1B)R BP(ND) values.
Twelve medication-free, recently abstinent (at least 4 weeks) patients with AD (mean age 35.2 +/- 10.2 years, 5 women) and 12 healthy control subjects (HC) (mean age 30.6 +/- 9.2 years, 5 women) completed [(11)C]P943 positron emission tomography on a high-resolution research tomograph. Individual magnetic resonance imaging scans were collected to exclude individuals with anatomical abnormalities and for coregistration. Imaging data were analyzed with a multilinear reference tissue model.
Ventral striatal 5-HT(1B)R BP(ND) values (2.01 +/- .57% and 1.55 +/- .09%, respectively; 29% between-group difference, p = .006) were increased in AD compared with HC subjects. No influence of demographic or clinical variables or amount of injected radiotracer was observed.
This study provides the first evidence that AD in humans is, like in rodent models, associated with increased levels of ventral striatal 5-HT(1B)Rs.
尽管动物模型表明,酒精依赖(AD)与血清素 1B 受体(5-HT1BR)数量的增加有关,但AD 患者的 5-HT1BR 水平尚未得到研究。选择性 5-HT1BR 拮抗剂放射性配体 [(11)C]P943,可通过正电子发射断层扫描进行体内评估中枢 5-HT1BR 结合潜能(BP(ND))。由于其在 AD 中的核心作用,我们特别关注腹侧纹状体 5-HT1BR BP(ND)值。
12 名无药物、近期戒断(至少 4 周)的 AD 患者(平均年龄 35.2 +/- 10.2 岁,5 名女性)和 12 名健康对照者(HC)(平均年龄 30.6 +/- 9.2 岁,5 名女性)在高分辨率研究断层扫描仪上完成了 [(11)C]P943 正电子发射断层扫描。采集个体磁共振成像扫描以排除有解剖异常者,并进行配准。使用多线性参考组织模型分析成像数据。
AD 患者的腹侧纹状体 5-HT1BR BP(ND)值(分别为 2.01 +/-.57%和 1.55 +/-.09%;29%的组间差异,p =.006)高于 HC 组。未观察到人口统计学或临床变量或注射示踪剂数量的影响。
这项研究首次提供了证据,表明人类 AD 与啮齿动物模型一样,与腹侧纹状体 5-HT1BR 水平升高有关。