伐尼克兰对重度饮酒者酒精显著性神经关联的影响。
Effects of Varenicline on Neural Correlates of Alcohol Salience in Heavy Drinkers.
作者信息
Vatsalya Vatsalya, Gowin Joshua L, Schwandt Melanie L, Momenan Reza, Coe Marion A, Cooke Megan E, Hommer Daniel W, Bartlett Selena, Heilig Markus, Ramchandani Vijay A
机构信息
Section on Human Psychopharmacology, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Vatsalya, Gowin, Coe, Cooke, and Ramchandani); Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Schwandt and Heilig); Section on Brain Electrophysiology and Imaging, Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland (Drs Momenan and Hommer); Translational Research Institute, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia (Dr Bartlett).V.V. current affiliation: University of Louisville and Robley Rex VAMC, Louisville, Kentucky.
出版信息
Int J Neuropsychopharmacol. 2015 Jul 25;18(12):pyv068. doi: 10.1093/ijnp/pyv068.
BACKGROUND
Preclinical and emerging clinical evidence indicates that varenicline, a nicotinic partial agonist approved for smoking cessation, attenuates alcohol seeking and consumption. Reductions of alcohol craving have been observed under varenicline treatment and suggest effects of the medication on alcohol reward processing, but this hypothesis remains untested.
METHODS
In this double-blind, placebo-controlled randomized experimental medicine study, 29 heavy drinkers underwent a functional magnetic resonance imaging scan after 2 weeks of varenicline (2mg/d) or placebo administration. During functional magnetic resonance imaging, participants performed the Alcohol-Food Incentive Delay task, where they could earn points for snacks or alcohol. At baseline and after 3 weeks of medication, participants underwent intravenous alcohol self-administration sessions in the laboratory.
RESULTS
During the functional magnetic resonance imaging scan, participants in the varenicline group (N=17) reported lower feelings of happiness and excitement on subjective mood scales when anticipating alcohol reward compared with the placebo group (N=12). Linear mixed effects analysis revealed that anticipation of alcohol reward was associated with significant blood oxygen level dependent activation of the ventral striatum, amygdala, and posterior insula in the placebo group; this activation was attenuated in the varenicline group. The varenicline group showed no difference in intravenous alcohol self-administration relative to the placebo group for either session. Participants with higher insula activation when anticipating alcohol reward showed higher alcohol self-administration behavior across groups.
CONCLUSIONS
Our findings suggest that varenicline decreases blood oxygen level dependent activation in striato-cortico-limbic regions associated with motivation and incentive salience of alcohol in heavy drinkers. This mechanism may underlie the clinical effectiveness of varenicline in reducing alcohol intake and indicates its potential utility as a pharmacotherapy for alcohol use disorders.
背景
临床前和新出现的临床证据表明，伐尼克兰（一种被批准用于戒烟的烟碱类部分激动剂）可减少对酒精的寻觅和摄入。在伐尼克兰治疗期间观察到酒精渴望的降低，提示该药物对酒精奖赏加工有影响，但这一假设尚未得到验证。
方法
在这项双盲、安慰剂对照的随机实验性医学研究中，29名重度饮酒者在接受伐尼克兰（2mg/天）或安慰剂治疗2周后进行了功能磁共振成像扫描。在功能磁共振成像期间，参与者执行酒精-食物激励延迟任务，在此任务中他们可以因零食或酒精获得积分。在基线期和药物治疗3周后，参与者在实验室进行静脉酒精自我给药实验。
结果
在功能磁共振成像扫描期间，与安慰剂组（N = 12）相比，伐尼克兰组（N = 17）的参与者在预期酒精奖赏时，主观情绪量表上报告的幸福感和兴奋感较低。线性混合效应分析显示，在安慰剂组中，预期酒精奖赏与腹侧纹状体、杏仁核和后岛叶的显著血氧水平依赖性激活相关；在伐尼克兰组中这种激活减弱。伐尼克兰组在静脉酒精自我给药实验中与安慰剂组相比，两个实验阶段均无差异。在预期酒精奖赏时岛叶激活较高的参与者在所有组中均表现出较高的酒精自我给药行为。
结论
我们的研究结果表明，伐尼克兰可降低与重度饮酒者酒精动机和激励显著性相关的纹状体-皮质-边缘区域的血氧水平依赖性激活。这一机制可能是伐尼克兰减少酒精摄入量临床有效性的基础，并表明其作为酒精使用障碍药物治疗的潜在效用。
Zotero 插件