Department of Psychiatry, University of Muenster, Muenster, Germany.
Neuropsychopharmacology. 2013 Jul;38(8):1401-8. doi: 10.1038/npp.2013.45. Epub 2013 Feb 12.
The upregulation of glutamatergic excitatory neurotransmission is thought to be partly responsible for the acute withdrawal symptoms and craving experienced by alcohol-dependent patients. Most physiological evidence supporting this hypothesis is based on data from animal studies. In addition, clinical data show that GABAergic and anti-glutamatergic drugs ameliorate withdrawal symptoms, offering indirect evidence indicative of glutamatergic hyperexcitability in alcohol-dependent subjects. We used proton magnetic resonance spectroscopy to quantify the glutamate (Glu) levels in healthy control subjects and in alcohol-dependent patients immediately after detoxification. The volumes of interest were located in the nucleus accumbens (NAcc) and the anterior cingulate cortex (ACC), which are two brain areas that have important functions in reward circuitry. In addition to Glu, we quantified the levels of combined Glu and glutamine (Gln), N-acetylaspartate, choline-containing compounds, and creatine. The Glu levels in the NAcc were significantly higher in patients than in controls. Craving, which was measured using the Obsessive Compulsive Drinking Scale, correlated positively with levels of combined Glu and Gln in the NAcc and in the ACC. The levels of all other metabolites were not significantly different between patients and controls. The increased Glu levels in the NAcc in alcohol-dependent patients shortly after detoxification confirm the animal data and suggest that striatal glutamatergic dysfunction is related to ethanol withdrawal. The positive correlation between craving and glutamatergic metabolism in both key reward circuitry areas support the hypothesis that the glutamatergic system has an important role in the later course of alcohol dependence with respect to abstinence and relapse.
谷氨酸能兴奋性神经递质的上调被认为是导致酒精依赖患者急性戒断症状和渴求的部分原因。支持这一假设的大多数生理证据都基于动物研究的数据。此外，临床数据表明 GABA 能和抗谷氨酸能药物可改善戒断症状，这为酒精依赖者中谷氨酸能过度兴奋提供了间接证据。我们使用质子磁共振波谱技术来定量检测健康对照组和酒精依赖患者在解毒后即刻的谷氨酸（Glu）水平。感兴趣区位于伏隔核（NAcc）和前扣带皮层（ACC），这两个脑区在奖励回路中具有重要功能。除了 Glu，我们还定量了 Glu 与谷氨酰胺（Gln）、N-乙酰天冬氨酸、含胆碱化合物和肌酸的混合物的水平。NAcc 中的 Glu 水平在患者中明显高于对照组。使用强迫性饮酒量表测量的渴求与 NAcc 和 ACC 中的 Glu 和 Gln 水平呈正相关。患者和对照组之间的所有其他代谢物水平没有显著差异。酒精依赖患者解毒后 NAcc 中 Glu 水平升高，证实了动物数据，并表明纹状体谷氨酸能功能障碍与乙醇戒断有关。在两个关键奖励回路区域中，渴求与谷氨酸代谢之间的正相关支持了这样一种假设，即谷氨酸能系统在酒精依赖的后期阶段（与戒断和复发有关）中具有重要作用。
