Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.
Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.
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DOI：
10.1001/archgenpsychiatry.2011.2094
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发表时间：
2012-10
影响因子：
--
通讯作者：
Miller AH
中科院分区：
文献类型：
--
作者：
Capuron L;Pagnoni G;Drake DF;Woolwine BJ;Spivey JR;Crowe RJ;Votaw JR;Goodman MM;Miller AH
炎性细胞因子或细胞因子诱导剂可以改变基底神经节活性，包括降低对奖赏刺激的反应性，这可能是由细胞因子对多巴胺功能的作用介导的。确定长期给予炎症细胞因子干扰素α是否会降低基底神经节对奖赏的反应，以及这种变化是否与突触前纹状体多巴胺功能降低和行为改变有关。横向和纵向研究。门诊研究单位和神经成像设施在埃默里大学，亚特兰大，格鲁吉亚。符合干扰素α治疗条件的医学稳定的慢性丙型肝炎病毒（HCV）感染成人。通过功能性磁共振成像、正电子发射断层扫描在尾状核和壳核中放射性标记的氟多巴F18（18F-dopa）的摄取和周转以及干扰素α诱导的抑郁、快感缺乏、疲劳和神经毒性测量享乐奖励任务期间腹侧纹状体的神经活动。与等待干扰素α治疗的HCV患者（n = 14）相比，接受干扰素α治疗4 - 6周的HCV患者（n = 14）在赌博任务的输赢条件下表现出腹侧纹状体的双侧激活显著减少。腹侧纹状体的激活减少反过来又与快感缺乏、抑郁和疲劳显著相关。在一项单独的纵向研究中，用干扰素α治疗4 - 6周的HCV患者（n=12）在尾状核和壳核以及在功能性磁共振成像研究中确定的相同腹侧纹状体区域中表现出显著增加的18 F-多巴摄取和减少的18 F-多巴周转。在干扰素α给药期间，18F-多巴摄取和转换的基线和百分比变化与行为改变相关，包括抑郁、疲劳和神经毒性。这些数据复制和扩展的结果，炎症刺激，包括炎性细胞因子，如干扰素α，改变基底神经节的活动和行为与突触前纹状体多巴胺功能的显着变化与多巴胺合成或释放减少一致。
Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function. To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior. Cross-sectional and longitudinal studies. Outpatient research unit and neuroimaging facilities at Emory University, Atlanta, Georgia. Medically stable adults with chronic hepatitis C virus (HCV) infection eligible for interferon alfa treatment. Neural activity in the ventral striatum during a hedonic reward task as measured by functional magnetic resonance imaging, uptake and turnover of radiolabeled fluorodopa F 18 (18F-dopa) in caudate and putamen using positron emission tomography, and interferon alfa–induced depression, anhedonia, fatigue, and neurotoxicity. Patients with HCV receiving interferon alfa for 4 to 6 weeks (n=14) exhibited significantly reduced bilateral activation of the ventral striatum in the win vs lose condition of a gambling task compared with patients with HCV awaiting interferon alfa treatment (n=14). Reduced activation of the ventral striatum was, in turn, significantly correlated with anhedonia, depression, and fatigue. In a separate longitudinal study, patients with HCV treated with interferon alfa for 4 to 6 weeks (n=12) exhibited significantly increased 18F-dopa uptake and decreased 18F-dopa turnover in caudate and putamen and in the same ventral striatal regions identified in the functional magnetic resonance imaging study. Baseline and percentage change in 18F-dopa uptake and turnover were correlated with behavioral alterations, including depression, fatigue, and neurotoxicity, during interferon alfa administration. These data replicate and extend findings that inflammatory stimuli, including inflammatory cytokines, such as interferon alfa, alter basal ganglia activity and behavior in association with significant changes in presynaptic striatal dopamine function consistent with decreased dopamine synthesis or release.
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影响因子：
4.7
作者：
HADJICONSTANTINOU, M;WEMLINGER, TA;NEFF, NH
通讯作者：
NEFF, NH
影响因子：
6.3
作者：
CUNNINGHAM, VJ;HUME, SP;JONES, AKP
通讯作者：
JONES, AKP
影响因子：
10.6
作者：
Capuron, Lucile;Schroecksnadel, Sebastian;Fuchs, Dietmar
通讯作者：
Fuchs, Dietmar
影响因子：
6.3
作者：
EIDELBERG, D;MOELLER, JR;FAHN, S
通讯作者：
FAHN, S
影响因子：
10.6
作者：
Brydon L;Harrison NA;Walker C;Steptoe A;Critchley HD
通讯作者：
Critchley HD