The effects of chronic alcohol self-administration on serotonin-1A receptor binding in nonhuman primates
The effects of chronic alcohol self-administration on serotonin-1A receptor binding in nonhuman primates
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DOI：
10.1016/j.drugalcdep.2014.08.015
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发表时间：
2014-11-01
影响因子：
4.2
通讯作者：
Christian, Bradley T.
中科院分区：
文献类型：
--
作者：
Hillmer, Ansel T.;Wooten, Dustin W.;Christian, Bradley T.
背景：先前的研究已经发现血清素系统和酒精自我管理之间的相互关系。这项工作的目的是直接观察恒河猴体内长期乙醇自我给药对5-羟色胺5-HT 1A受体结合[F-18]mefway PET神经成像的影响。受试者首先成像酒精幼稚，并再次在慢性乙醇自我管理，以量化5-HT 1A受体binding.Methods的变化：14恒河猴受试者（10.7-12.8岁）进行基线[F-18]MEFWAY PET扫描之前，酒精暴露。受试者随后在4个月内逐渐增加乙醇剂量作为诱导期，随后立即进行至少9个月的自由饮用乙醇。在随意乙醇自我给药的最后三个月期间获得[18 F]mefway后PET扫描。以小脑为参照区，用结合电位（BPND）测定5-HT 1A受体结合。在5-HT 1A结合在慢性乙醇自我管理过程中的变化进行了检查。结合指标与每日乙醇自我administration.Results的关系也进行了评估：广泛增加5-HT 1A结合慢性乙醇自我管理期间观察到，独立的乙醇消耗量。中缝核和平均每日乙醇自我管理之间的正相关性也观察到，表明基线5-HT 1A结合在这一地区预测drinking levels.Conclusions：5-HT 1A结合水平的增加在慢性乙醇自我管理过程中表现出一个重要的调制的5-羟色胺系统由于慢性酒精暴露。此外，5-HT 1A结合中缝核和每日乙醇自我管理之间的相关性表明5-羟色胺系统和酒精自我管理之间的关系。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Background: Previous studies have found interrelationships between the serotonin system and alcohol self-administration. The goal of this work was to directly observe in vivo effects of chronic ethanol self-administration on serotonin 5-HT1A receptor binding with [F-18]mefway PET neuroimaging in rhesus monkeys. Subjects were first imaged alcohol-naive and again during chronic ethanol self-administration to quantify changes in 5-HT1A receptor binding.Methods: Fourteen rhesus monkey subjects (10.7-12.8 years) underwent baseline [F-18]mefway PET scans prior to alcohol exposure. Subjects then drank gradually increasing ethanol doses over four months as an induction period, immediately followed by at least nine months ad libidum ethanol access. A post [18F]mefway PET scan was acquired during the final three months of ad libidum ethanol self-administration. 5-HT1A receptor binding was assayed with binding potential (BPND) using the cerebellum as a reference region. Changes in 5-HT1A binding during chronic ethanol self-administration were examined. Relationships of binding metrics with daily ethanol self-administration were also assessed.Results: Widespread increases in 5-HT1A binding were observed during chronic ethanol self-administration, independent of the amount of ethanol consumed. A positive correlation between 5-HT1A binding in the raphe nuclei and average daily ethanol self-administration was also observed, indicating that baseline 5-HT1A binding in this region predicted drinking levels.Conclusions: The increase in 5-HT1A binding levels during chronic ethanol self-administration demonstrates an important modulation of the serotonin system due to chronic alcohol exposure. Furthermore, the correlation between 5-HT1A binding in the raphe nuclei and daily ethanol self-administration indicates a relationship between the serotonin system and alcohol self-administration. (C) 2014 Elsevier Ireland Ltd. All rights reserved.