Discipline of Addiction Medicine, Central Clinical School, Faculty of Medicine and Health, University of Sydney, Lv 6, King George V Building, 83-117 Missenden Rd, Camperdown, NSW, 2050, Australia.
Central Clinical School, Faculty of Medicine and Health, & Centre for Translational Data Science, University of Sydney, Sydney, NSW, Australia.
Psychopharmacology (Berl). 2021 May;238(5):1291-1302. doi: 10.1007/s00213-019-05192-5. Epub 2019 Feb 20.
Baclofen has been shown to effect fMRI alcohol cue reactivity in alcohol dependence, but potential varying effects related to baclofen dose levels have not been examined.
This study investigated whether baclofen attenuates craving and alcohol cue-elicited activation in alcohol-dependent treatment seekers, and the relationship between this response and clinical outcomes (Morley et al. 2018; Morley et al. 2013).
Participants included 30 alcohol-dependent individuals who had received daily baclofen 30 mg (n = 11), 75 mg (n = 8) or placebo (n = 11) for at least 2 weeks. Using functional magnetic resonance imaging (fMRI), we examined alcohol cue-elicited neural activation during a visual alcohol cue reactivity task 120 min following treatment administration, and alcohol cue reactivity and percentage of heavy drinking days (% HDD) associations were assessed.
Both baclofen-treated groups reported fewer post-scan % HDD when compared to the placebo-treated group, but no subjective craving group differences were found. Increased alcohol cue-elicited activation was seen in placebo compared to the 75 mg/day baclofen participants in two clusters spanning prefrontal regions implicated in cue reactivity, chiefly frontal regions (i.e., frontal and precentral gyri, anterior cingulate cortex), but no observed alcohol cue reactivity differences between placebo and 30 mg/day baclofen groups. Post-scan % HDD was positively correlated with increased alcohol cue-elicited activation in a cluster encompassing the bilateral caudate nucleus and dorsal anterior cingulate cortex when comparing placebo versus 75 mg/day baclofen groups, and several clusters including prefrontal and mesolimbic regions when comparing placebo versus 30 mg/day baclofen groups.
Baclofen administration attenuates alcohol cue-elicited activation and reduced the association in baclofen-treated participants between increased activity in key drug cue reactivity regions and higher post-scan % HDD observed in placebo-treated participants, suggesting a dose-specific response effect that may lead to reduced heavy drinking in chronic alcohol-dependent individuals.
ClinicalTrials.gov , NCT01711125, https://clinicaltrials.gov/ct2/show /NCT01711125.
巴氯芬已被证明可影响酒精依赖患者的 fMRI 酒精线索反应，但尚未研究剂量水平与巴氯芬相关的潜在不同作用。
本研究旨在探讨巴氯芬是否能减轻酒精依赖治疗寻求者的渴求感和酒精线索诱发的激活，以及这种反应与临床结果的关系（Morley 等人，2018 年；Morley 等人，2013 年）。
参与者包括 30 名接受每日巴氯芬 30mg（n=11）、75mg（n=8）或安慰剂（n=11）治疗至少 2 周的酒精依赖个体。使用功能磁共振成像（fMRI），我们在治疗后 120 分钟检查了视觉酒精线索反应任务期间的酒精线索诱发的神经激活，并评估了酒精线索反应和大量饮酒天数的百分比（%HDD）的关联。
与安慰剂组相比，两组巴氯芬治疗组报告的扫描后 %HDD 较少，但未发现主观渴求组的差异。与 75mg/天巴氯芬组相比，安慰剂组在两个跨越涉及线索反应的额前区域的簇中显示出更强的酒精线索诱发的激活，主要是额前区域（即额和中央前回、前扣带皮质），但在安慰剂组和 30mg/天巴氯芬组之间没有观察到酒精线索反应的差异。与安慰剂相比，扫描后 %HDD 与双侧尾状核和背侧前扣带皮质的一个簇中的酒精线索诱发的激活呈正相关，当比较 75mg/天巴氯芬组时，与安慰剂相比，几个簇包括额前和中边缘区域，当比较 30mg/天巴氯芬组时。
巴氯芬给药可减弱酒精线索诱发的激活，并降低在接受巴氯芬治疗的参与者中观察到的关键药物线索反应区域活性增加与安慰剂治疗参与者中扫描后 %HDD 增加之间的关联，表明存在剂量特异性反应效应，可能导致慢性酒精依赖个体饮酒量减少。
ClinicalTrials.gov，NCT01711125，https://clinicaltrials.gov/ct2/show/NCT01711125。
