Lee Tse-Ang, Lee Hongjoo J, Mangieri Regina A, Gonzales Rueben, Ajmal Heba, Hutter Tanya
Department of Mechanical Engineering, The University of Texas at Austin, Austin, TX 78712, USA.
Department of Psychology, The University of Texas at Austin, Austin, TX 78712, USA.
Alcohol. 2025 Mar;123:69-76. doi: 10.1016/j.alcohol.2024.09.001. Epub 2024 Sep 6.
The unclear mechanisms of ethanol metabolism in the brain highlight the need for a deeper understanding of its metabolic pathways. This study used in vivo microdialysis to simultaneously sample ethanol and its metabolites, acetaldehyde and acetate, in the rat striatum following self-administration of ethanol, emphasizing the natural oral exposure route. To enhance the self-administration, rats underwent two-bottle-choice and limited access training. Dialysate samples, collected every 10 min for 2.5 h, were analyzed using gas chromatography with flame ionization detection (GC-FID). The measured time courses of dialysate concentrations of ethanol, acetaldehyde, and acetate provided insights into dynamics of ethanol metabolism. Notably, in a subject with low ethanol consumption (0.29 g/kg), the concentration of acetaldehyde remained below the limit of detection throughout the experiment. However, the acetate concentration was clearly increased after ethanol consumption in this subject and was comparable to that of other rats with higher ethanol consumption. Compared with focusing only on peak values in the time-courses of concentrations of ethanol and its metabolites, calculating areas under curves provided better models of the relationships between ethanol intake and individual ethanol metabolites, as indicated by the R-square values for the linear regressions. This approach of using the area under the curve accounts for both the amplitude and duration of the concentration profiles, reducing the impact of variations in individual drinking patterns. In vivo microdialysis enables concurrent sampling of brain metabolites during oral ethanol administration, contributing insights into metabolite dynamics. To our knowledge, this paper is the first to report measurement of all three analytes in the brain following self-administration of ethanol. Future studies will explore regional variations and dynamics post-ethanol dependence, further advancing our understanding of ethanol metabolism in the brain.
大脑中乙醇代谢机制尚不清楚，这凸显了深入了解其代谢途径的必要性。本研究采用体内微透析技术，在大鼠经口自行摄入乙醇后，同时采集其纹状体中的乙醇及其代谢产物乙醛和乙酸盐，强调了自然经口暴露途径。为增强自行摄入乙醇的行为，大鼠接受了双瓶选择和限时摄入训练。每隔10分钟采集一次透析液样本，共采集2.5小时，采用火焰离子化检测气相色谱法（GC-FID）进行分析。所测得的乙醇、乙醛和乙酸盐透析液浓度随时间变化的过程，为乙醇代谢动态提供了见解。值得注意的是，在乙醇摄入量较低（0.29克/千克）的实验对象中，整个实验过程中乙醛浓度均低于检测限。然而，该实验对象摄入乙醇后，乙酸盐浓度明显升高，且与其他乙醇摄入量较高的大鼠相当。与仅关注乙醇及其代谢产物浓度随时间变化过程中的峰值相比，计算曲线下面积能更好地建立乙醇摄入量与各乙醇代谢产物之间的关系模型，线性回归的决定系数（R平方值）表明了这一点。这种使用曲线下面积的方法兼顾了浓度曲线的幅度和持续时间，减少了个体饮酒模式差异的影响。体内微透析能够在经口给予乙醇期间同时采集脑代谢产物，有助于深入了解代谢产物动态。据我们所知，本文首次报道了乙醇自行摄入后大脑中所有三种分析物的测量结果。未来的研究将探索乙醇依赖后的区域差异和动态变化，进一步加深我们对大脑中乙醇代谢的理解。
