Addiction Neuroscience, Department of Psychology and Indiana Alcohol Research Center, Indiana University - Purdue University Indianapolis, Indianapolis, Indiana, USA.
Department of Basic Medical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Addict Biol. 2024 Sep;29(9):e13434. doi: 10.1111/adb.13434.
Frontloading is an alcohol drinking pattern where intake is skewed towards the onset of access. This study aimed to identify brain regions involved in frontloading. Whole brain imaging was performed in 63 C57Bl/6J (32 female, 31 male) mice that underwent 8 days of binge drinking using drinking-in-the-dark (DID). On Days 1-7 mice received 20% (v/v) alcohol or water for 2 h. Intake was measured in 1-min bins using volumetric sippers. On Day 8 mice were perfused 80 min into the DID session and brains were extracted. Brains were processed to stain for Fos protein using iDISCO+. Following light sheet imaging, ClearMap2.1 was used to register brains to the Allen Brain Atlas and detect Fos+ cells. For network analyses, Day 8 drinking patterns were used to characterize mice as frontloaders or non-frontloaders using a change-point analysis. Functional correlation matrices were calculated for each group from log Fos values. Euclidean distances were calculated from these R values and clustering was used to determine modules (highly connected groups of brain regions). In males, alcohol access decreased modularity (three modules in both frontloaders and non-frontloaders) as compared to water (seven modules). In females, an opposite effect was observed. Alcohol access (nine modules for frontloaders) increased modularity as compared to water (five modules). Further, different brain regions served as hubs in frontloaders as compared to control groups. In conclusion, alcohol consumption led to fewer, but more densely connected, groups of brain regions in males but not females and we identify several brain-wide signatures of frontloading.
前置饮酒是一种饮酒模式，其中摄入偏向于开始饮酒。本研究旨在确定与前置饮酒相关的大脑区域。对 63 只 C57Bl/6J 小鼠（32 只雌性，31 只雄性）进行全脑成像，这些小鼠在暗饮（DID）中经历了 8 天的狂欢饮酒。在第 1-7 天，小鼠接受 20%（v/v）酒精或水，持续 2 小时。使用容量吸管以 1 分钟的间隔测量摄入量。在第 8 天，小鼠在 DID 期间的 80 分钟内进行灌注，然后提取大脑。大脑被处理以使用 iDISCO+对 Fos 蛋白进行染色。在光片成像后，使用 ClearMap2.1 将大脑注册到 Allen 大脑图谱并检测 Fos+细胞。对于网络分析，使用变化点分析根据第 8 天的饮酒模式将小鼠归类为前置饮酒者或非前置饮酒者。从 log Fos 值计算每组的功能相关矩阵。从这些 R 值计算欧几里得距离，并使用聚类来确定模块（大脑区域的高度连接组）。在雄性中，与水相比，酒精摄入降低了模块性（前置饮酒者和非前置饮酒者均为三个模块）。在雌性中，观察到相反的效果。与水相比，酒精摄入（前置饮酒者为九个模块）增加了模块性（五个模块）。此外，与对照组相比，前置饮酒者的不同大脑区域充当了枢纽。总之，酒精摄入导致雄性中更少但更密集连接的大脑区域组，但在雌性中则没有，并且我们确定了几个与前置饮酒相关的全脑特征。
