动物和人类证据支持催产素在寻求酒精行为中的作用。有兴趣,因此,靶向催产素途径作为治疗酒精使用障碍的新的药理学方法。为此,重要的是要了解酒精使用障碍对脑区内源性催产素的影响,这些脑区与酒精使用障碍的开始和维持有关。与非酒精依赖的男性对照(n=16)相比,我们检查了酒精使用障碍男性(n=11)的人类死后脑组织。我们先验地针对啮齿动物研究中的五个大脑区域,是催产素神经元的投影区域:伏隔核,杏仁核,海马体,腹侧被盖区和前额叶皮质。在所研究的每个脑区域中测量催产素肽和受体的mRNA水平的倍数变化。与对照组相比,酒精使用障碍受试者的前额叶皮层中催产素肽mRNA的倍数变化显着升高(未校正的p=0.0001;FDR校正的p=0.001)。对于27名受试者的整个样本,前额叶皮层催产素肽mRNA的倍数变化与每日酒精摄入量(r2=0.38;p=0.002)和每周饮料(r2=0.24;p=0.02)之间存在显着正相关。根据先前的动物和人类文献,讨论了内源性催产素系统随慢性酒精暴露的变化而变化的结果。
Animal and human evidence supports a role for oxytocin in alcohol-seeking behaviors. There is interest, therefore, in targeting the oxytocin pathway as a new pharmacologic approach to treat alcohol use disorder. To this end, it is important to understand the effect of alcohol use disorder on endogenous oxytocin in brain regions that are relevant for the initiation and maintenance of alcohol use disorder. We examined human post-mortem brain tissue from males with alcohol use disorder (n=11) compared to nonalcohol dependent male controls (n=16). We a priori targeted five brain regions that in rodent studies, are projection areas for oxytocin neurons: nucleus accumbens, amygdala, hippocampus, ventral tegmental area and prefrontal cortex. Fold change in mRNA levels of oxytocin peptide and receptor were measured in each of the brain regions studied. Fold change for oxytocin peptide mRNA was significantly elevated in the prefrontal cortex of subjects with alcohol use disorder compared to controls (uncorrected p=0.0001; FDR-corrected p=0.001). For the entire sample of 27 subjects, there was a significant positive correlation between the fold change in oxytocin peptide mRNA in the prefrontal cortex and both daily alcohol intake (r2=0.38; p=0.002) and drinks per week (r2=0.24; p=0.02). Results are discussed in light of the previous animal and human literature on changes in the endogenous oxytocin system as an effect of chronic alcohol exposure.