Cheng Hu, Kellar Derek, Lake Allison, Finn Peter, Rebec George V, Dharmadhikari Shalmali, Dydak Ulrike, Newman Sharlene
Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
School of Health Sciences, Purdue University, West Lafayette, IN, USA.
Alcohol Alcohol. 2018 May 1;53(3):209-215. doi: 10.1093/alcalc/agx119.
Growing evidence suggests that glutamate neurotransmission plays a critical role in alcohol addiction. Cue-induced change of glutamate has been observed in animal studies but never been investigated in humans. This work investigates cue-induced change in forebrain glutamate in individuals with alcohol use disorder (AUD). A total of 35 subjects (17 individuals with AUD and 18 healthy controls) participated in this study. The glutamate concentration was measured with single-voxel 1H-MR spectroscopy at the dorsal anterior cingulate. Two MRS sessions were performed in succession, the first to establish basal glutamate levels and the second to measure the change in response to alcohol cues. The changes in glutamate were quantified for both AUD subjects and controls. A mixed model ANOVA and t-tests were performed for statistical analysis. ANOVA revealed a main effect of cue-induced decrease of glutamate level in the anterior cingulate cortex (ACC). A significant interaction revealed that only AUD subjects showed significant decrease of glutamate in the ACC. There were no significant group differences in the level of basal glutamate. However, a negative correlation was found between the basal glutamate level and the number of drinking days in the past 2 weeks for the AUD subjects. Collectively, our results indicate that glutamate in key areas of the forebrain reward circuit is modulated by alcohol cues in early alcohol dependence.
越来越多的证据表明,谷氨酸神经传递在酒精成瘾中起着关键作用。在动物研究中已观察到线索诱导的谷氨酸变化,但从未在人类中进行过研究。这项工作研究了酒精使用障碍(AUD)个体中线索诱导的前脑谷氨酸变化。共有35名受试者(17名AUD个体和18名健康对照)参与了这项研究。使用单体素1H-MR波谱在背侧前扣带回测量谷氨酸浓度。连续进行两次MRS检查,第一次确定基础谷氨酸水平,第二次测量对酒精线索的反应变化。对AUD受试者和对照组的谷氨酸变化进行了量化。进行了混合模型方差分析和t检验以进行统计分析。方差分析显示线索诱导的前扣带回皮质(ACC)谷氨酸水平降低有主效应。显著的交互作用表明,只有AUD受试者的ACC中谷氨酸显著降低。基础谷氨酸水平在两组之间没有显著差异。然而,在AUD受试者中,基础谷氨酸水平与过去2周的饮酒天数之间存在负相关。总体而言,我们的结果表明,在前脑奖赏回路的关键区域,谷氨酸在酒精依赖早期会受到酒精线索的调节。