Dysfunctional interaction of dopamine and glutamate as a predictor for the development of alcohol use disorders (AUD)

尽管有负面后果，但饮酒可能依赖于使行为适应环境变化的灵活性受损，即对奖励偶发事件的反应学习。这种学习缺陷具有临床相关性，特别是在治疗期间和心理社会结果中。在PET调查中观察到的解毒酒精依赖患者中中枢多巴胺d2受体的可用性降低及其对奖励相关学习的假设影响与低多巴胺能状态下学习缺陷的证据一致，特别是对非依赖样本的回避学习。越来越多的证据表明，与学习相关的纹状体多巴胺信号是由高级执行功能调节的，例如前额皮质。在这里，前额叶皮层广泛的谷氨酸能输出对于皮层下学习机制至关重要，并且与最近的多巴胺-谷氨酸相互作用功能障碍模型和酒精依赖的神经营养信号模型相匹配。在本项目中，多巴胺与谷氨酸相互作用对学习缺陷和连续复发概率的影响是通过[18F]fallypride PET和磁共振波谱（MRS）测量谷氨酸绝对浓度来确定的。

Alcohol consumption despite negative consequences may rely on impaired flexibility in adapting the behavior to environmental changes, i.e. learning in response to reward contingencies. This learning deficit is of clinical relevance particularly during therapy and for the psychosocial outcome. The reduced availability of central dopamine D2-receptors in detoxified alcohol dependent patients observed in PET investigations and their hypothetical effects on reward-related learning are in line with evidence for learning deficits in hypodopaminergic states, particularly for avoidance learning in non-dependent samples. Growing evidence indicates that the learning-related striatal dopamine signals are modulated by higher executive functions involving, e.g., the prefrontal cortex. Here, broad glutamatergic outputs of the prefrontal cortex are crucial for subcortical learning mechanisms and match with recent models of interactive dopamine-glutamate dysfunctions and models of neurotrophic signaling in alcohol dependence. In this project, the impact of the dopamine x glutamate interaction on learning deficits and consecutive relapse probability is targeted with [18F]fallypride PET and the measurement of absolute concentrations of glutamate with magnetic resonance spectroscopy (MRS).