Alvanzo Anika A H, Wand Gary S, Kuwabara Hiroto, Wong Dean F, Xu Xiaoqiang, McCaul Mary E
Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Addict Biol. 2017 Jan;22(1):218-228. doi: 10.1111/adb.12300. Epub 2015 Sep 29.
The aim of this study was to examine the relationship between family history of alcohol use disorder and striatal dopamine using positron emission tomography imaging. Participants were 84 healthy, 18- to 30-year-old, social drinkers recruited via fliers and newspaper advertisements. At assessment, participants completed measures of lifetime personal and family substance use and psychiatric symptoms. Participants underwent two consecutive positron emission tomography scans using the D /D dopamine receptor radioligand [ C]raclopride. Scans were preceded by intravenous saline and amphetamine 0.3 mg/kg, providing measures of baseline [ C]raclopride binding potential (BP ) and change in [ C]raclopride (ΔBP ). Subjective ratings of stimulant drug effects were collected during scans. Subjects were classified as family history positive (FHP) if they reported any first-degree relative with alcohol use disorder (AUD) and family history negative (FHN) if no first-degree relatives had history of AUD. Participants were predominantly White (69.0 percent) and male (62.1 percent). Baseline [ C]raclopride BP was generally higher in FHP compared with FHN subjects across striatal subdivisions. There were no differences in ΔBP across regions. Negative subjective drug effects were more pronounced in FHP than in FHN subjects. While FHN subjects evidenced the expected positive relationship between ΔBP and positive subjective drug effects, this relationship was disrupted in FHP subjects. There are key differences in dopamine status and subjective stimulant drug experiences as a function of family AUD history. These findings have important implications for understanding risk for AUD development in FHP offspring.
本研究的目的是使用正电子发射断层扫描成像技术来检测酒精使用障碍家族史与纹状体多巴胺之间的关系。参与者是通过传单和报纸广告招募的84名健康的18至30岁社交饮酒者。在评估时,参与者完成了终身个人和家庭物质使用及精神症状的测量。参与者使用D /D多巴胺受体放射性配体[ C]雷氯必利连续进行了两次正电子发射断层扫描。扫描前先静脉注射生理盐水和0.3mg/kg苯丙胺,以测量基线[ C]雷氯必利结合潜力(BP)和[ C]雷氯必利的变化(ΔBP)。在扫描过程中收集了对刺激性药物效果的主观评分。如果参与者报告有任何患有酒精使用障碍(AUD)的一级亲属,则将其分类为家族史阳性(FHP);如果没有一级亲属有AUD病史,则分类为家族史阴性(FHN)。参与者主要是白人(69.0%)和男性(62.1%)。在整个纹状体亚区,FHP受试者的基线[ C]雷氯必利BP通常高于FHN受试者。各区域的ΔBP没有差异。FHP受试者的负面主观药物效果比FHN受试者更明显。虽然FHN受试者的ΔBP与积极的主观药物效果之间呈现出预期的正相关关系,但这种关系在FHP受试者中被破坏了。作为家族AUD病史的一个函数因素,多巴胺状态和主观刺激性药物体验存在关键差异。这些发现对于理解FHP后代发生AUD的风险具有重要意义。