Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular, cerebral metabotropic glutamate receptor 5 (mGluR5). ¹⁸F-3-fluoro-5-[(pyridin-3-yl)ethynyl]benzonitrile (¹⁸F-FPEB) PET has revealed that chronic alcohol use leads to decreased limbic mGluR5 availability, which was associated with less craving. Here, we tested whether the state of decreased mGluR5 availability in alcohol-dependent patients normalizes during abstinence (at 2 and 6 mo of detoxification) and whether initial mGluR5 imaging parameters can predict individual relapse. Methods: ¹⁸F-FPEB scans were performed for 16 recently detoxified alcohol-dependent patients (baseline condition), 2 mo after detoxification (n = 10), and 6 mo after detoxification (n = 8); 32 age- and sex-matched controls were included for comparison. mGluR5 availability was quantified by the ¹⁸F-FPEB total distribution volume using both voxel-by-voxel and volume-of-interest analyses. During follow-up, craving was assessed using the Desire for Alcohol Questionnaire, and alcohol consumption was assessed using the timeline follow-back method and monitored by hair ethyl glucuronide analysis. Results: During abstinence, alcohol-dependent patients showed sustained recovered mGluR5 availability in cortical and subcortical regions compared with the baseline, up to the levels observed in controls, after 6 mo in most areas except for the hippocampus, nucleus accumbens, and thalamus. Higher striatopallidal mGluR5 availability was observed at the baseline in patients who had a relapse during the 6-mo follow-up period (+25.1%). Also, normalization of striatal mGluR5 to control levels was associated with reduced craving (“desire and intention to drink” and “negative reinforcement”; r = 0.72–0.94). Conclusion: Reduced cerebral mGluR5 availability in alcohol-dependent patients recovers during abstinence and is associated with reduced craving. Higher striatal mGluR5 availability in alcohol-dependent users may be associated with long-term relapse.

酒精依赖和复发的动物模型证明了谷氨酸能系统，特别是脑代谢型谷氨酸受体5（mGluR5）的重要作用。¹⁸ F-3-氟-5-[（吡啶-3-基）乙炔基]苄腈（¹⁸ F-FPEB）PET显示，长期饮酒会导致边缘mGluR5可用性降低，这与较少的渴望有关。在这里，我们测试了酒精依赖患者的mGluR5可用性降低状态是否在戒酒期间（排毒2和6 mo）正常化，并且初始mGluR5成像参数是否可以预测个体复发。方法： 对16名最近解毒的酒精依赖患者（基线情况）进行^18次F-FPEB扫描，解毒后2个月（n = 10），排毒后6 mo（n = 8）；包括32个年龄和性别匹配的对照进行比较。mGluR5的可用性通过¹⁸ F-FPEB总分布量（使用逐个体素和兴趣量分析）进行量化。在随访期间，使用“酒精问卷调查表”评估渴望，并使用时间轴跟踪方法评估饮酒量，并通过毛发乙基葡糖醛酸苷分析进行监测。结果：在戒酒期间，酒精依赖的患者在皮层和皮层下区域显示出与基线相比持续恢复的mGluR5可用性，达到对照水平，在海马，伏隔核和丘脑以外的大多数区域中，至少6 mo之后。在基线的6个月随访期间复发的患者中，纹状体外膜mGluR5的利用率更高（+ 25.1％）。同样，纹状体mGluR5正常化至控制水平也与渴望减少有关（“欲望和饮酒意图”和“负性增强”；r = 0.72-0.94）。结论：酒精依赖患者的脑mGluR5可用性降低会在禁欲期间恢复，并与渴望降低有关。酒精依赖型用户纹状体mGluR5的更高可用性可能与长期复发有关。