Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder.
Reduced ventral striatal/ventral pallidal serotonin1B receptor binding potential in major depressive disorder.
复制标题
DOI：
10.1007/s00213-010-1881-0
复制
发表时间：
2011-02
影响因子：
3.4
通讯作者：
Neumeister, Alexander
中科院分区：
文献类型：
--
作者：
Murrough, James W.;Henry, Shannan;Hu, Jian;Gallezot, Jean-Dominique;Planeta-Wilson, Beata;Neumaier, John F.;Neumeister, Alexander
关键词：
尽管5-羟色胺（5-HT）失调与重性抑郁症（MDD）的病理生理学有关，但特定受体亚型的作用仍有待阐明。新兴的临床前研究表明，5-HT 1B受体在行为调节和抑郁表型中发挥重要作用。特别是，位于纹状体内的5-HT 1B异源受体已被证明在抗抑郁作用中发挥重要作用。本研究的目的是确定5-HT 1B受体结合电位（BPND）在该地区的腹侧纹状体/腹侧苍白球（VS/VP）的个人与MDD和健康对照参与者。10名患有重度抑郁发作（MDE）的MDD受试者（30.8±9.5岁，5名男性/5名女性）和10名健康对照受试者（30.7±10.5岁，5名男性/5名女性）使用选择性5-HT 1B受体放射性配体[11 C]P943进行正电子发射断层扫描（PET）。在感兴趣的VS/VP区域内，MDD组的[11 C]P943 BPND显著低于健康对照组（分别为1.37±0.13和1.68±0.16;组间差异为18.7%; p<0.001）。与临床前和尸检数据一致，我们的研究结果表明MDD患者VS/VP 5-HT 1B受体功能异常降低。异常的5-HT 1B异源受体功能可能通过与多巴胺、γ-氨基丁酸或谷氨酸系统的相互作用，导致纹状体（包括延髓核）内的奖励信号传导功能障碍。我们的研究结果表明，减少5-HT 1B受体信号转导的VS/VP在MDD和有助于测试5-HT 1B激动剂作为一种新型的抗抑郁药的治疗原理。
Although serotonin (5-HT) dysregulation is implicated in the pathophysiology of major depressive disorder (MDD), the role of specific receptor subtypes remains to be elucidated. Emerging preclinical research suggests an important role for the 5-HT1B receptor in behavioral regulation and depressive phenotypes. In particular, 5-HT1B heteroreceptors located within the striatum have been shown to play an essential role in antidepressant action. The objective of this study was to determine 5-HT1B receptor binding potential (BPND) in the region of the ventral striatum/ventral pallidum (VS/VP) in individuals with MDD and healthy control participants. Ten participants with MDD (30.8±9.5 years, five men/five women) in a current major depressive episode (MDE) and ten healthy control participants (30.7±10.5 years, five men/five women) underwent positron emission tomography (PET) scanning with the selective 5-HT1B receptor radioligand [11C]P943. Within the VS/VP region of interest, [11C]P943 BPND was significantly reduced in the MDD group compared with the healthy control group (1.37±0.13 and 1.68±0.16, respectively; 18.7% between-group difference; p<0.001). Consistent with preclinical and postmortem data, our findings suggest abnormally reduced function of VS/VP 5-HT1B receptors in humans with MDD. Abnormal 5-HT1B heteroreceptor function may contribute to dysfunctional reward signaling within the striatum, including the nucleus accumbens, via interaction with dopamine, γ-amino-butyric acid, or glutamate systems. Our findings suggest reduced 5-HT1B receptor signaling in the VS/VP in MDD and contribute to the therapeutic rationale for testing 5-HT1B agonists as a novel class of antidepressants.
登录
查看更多内容
影响因子：
--
作者：
Neumeister, A;Nugent, AC;Drevets, WC
通讯作者：
Drevets, WC
影响因子：
4.7
作者：
Carlezon WA Jr;Thomas MJ
通讯作者：
Thomas MJ
影响因子：
3.1
作者：
Nabulsi, Nabeel;Huang, Yiyun;Ding, Yu-Shin
通讯作者：
Ding, Yu-Shin
影响因子：
3.1
作者：
Drevets, Wayne C.;Thase, Michael E.;Mathis, Chester
通讯作者：
Mathis, Chester
影响因子：
64.8
作者：
Krishnan, Vaishnav;Nestler, Eric J.
通讯作者：
Nestler, Eric J.