Discipline of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, NSW, Australia; Edith Collins Centre (Translational Research in Alcohol, Drugs and Toxicology), Sydney Local Health District, Sydney, NSW, Australia.
Discipline of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, NSW, Australia; Drug Health Services, Royal Prince Alfred Hospital, NSW, Australia; Edith Collins Centre (Translational Research in Alcohol, Drugs and Toxicology), Sydney Local Health District, Sydney, NSW, Australia.
Eur Neuropsychopharmacol. 2021 May;46:28-36. doi: 10.1016/j.euroneuro.2021.02.010. Epub 2021 Mar 15.
The GABA agonist, baclofen, has been shown to reduce alcohol consumption in patients with alcohol use disorder and also those with comorbid anxiety. This study aimed to evaluate the effect of baclofen versus placebo on the BOLD response during an anticipatory anxiety fMRI task in treatment seeking alcohol patients. Participants included 28 alcohol dependant individuals who had received daily baclofen 30 mg (n = 10), 75 mg (n = 8) or placebo (n = 10) for at least 2 week on a randomized controlled trial (Morley, Leung et al. 2013, Morley, Baillie et al. 2018). Using functional magnetic resonance imaging (fMRI), we examined threat cue-elicited neural activation during a threat reactivity task 120 min following administration of BAC (30 mg or 75 mg) or placebo. Whole-brain analyses revealed no significant differences between the combined BAC doses versus PL. However, there were significant decreases in anticipatory threat cue-elicited activation observed in BAC 75 mg/day compared to PL participants in the insula. In response to threat cues, high dose (75 mg/day) baclofen administration attenuates activation in the insula and inferior frontal gyrus, relative to placebo. These preliminary findings suggests that modulating emotional regulation and attentional allocation during high threat stimuli may be mediated by GABA receptors and may be a potential mechanism of action for baclofen's beneficial treatment effects for alcohol use disorder.
GABA 激动剂巴氯芬已被证明可减少酒精使用障碍患者和伴有共病焦虑症患者的饮酒量。本研究旨在评估在寻求酒精治疗的患者中，巴氯芬与安慰剂对预期性焦虑 fMRI 任务期间的 BOLD 反应的影响。参与者包括 28 名酒精依赖个体，他们在一项随机对照试验中接受了每日巴氯芬 30mg（n=10）、75mg（n=8）或安慰剂（n=10）治疗至少 2 周（Morley、Leung 等人，2013 年；Morley、Baillie 等人，2018 年）。使用功能磁共振成像（fMRI），我们在给药后 120 分钟检查了威胁线索诱发的神经激活在威胁反应任务期间。全脑分析显示，联合 BAC 剂量与 PL 之间没有显着差异。然而，与 PL 参与者相比，每日 75mg BAC 组观察到岛叶的预期威胁线索诱发的激活显着降低。在对威胁线索的反应中，与安慰剂相比，高剂量（75mg/天）巴氯芬给药可减轻岛叶和下额回的激活。这些初步发现表明，调节高威胁刺激期间的情绪调节和注意力分配可能是由 GABA 受体介导的，并且可能是巴氯芬对酒精使用障碍有益治疗效果的潜在作用机制。
