Recovery of Decreased Metabotropic Glutamate Receptor 5 Availability in Abstinent Alcohol-Dependent Patients
Recovery of Decreased Metabotropic Glutamate Receptor 5 Availability in Abstinent Alcohol-Dependent Patients
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DOI：
10.2967/jnumed.119.228825
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发表时间：
2020-02-01
影响因子：
9.3
通讯作者：
Van Laere, Koen
中科院分区：
文献类型：
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作者：
Ceccarini, Jenny;Leurquin-Sterk, Gil;Van Laere, Koen
酒精依赖和复发的动物模型证明了谷氨酸能系统的重要作用，特别是大脑代谢型谷氨酸受体5（mGluR 5）。F-18-3-氟-5-[（吡啶3-基）乙炔基]苯甲腈（F-18-FPEB）PET显示，长期饮酒导致边缘mGluR 5可用性降低，这与渴望减少有关。在这里，我们测试了酒精依赖患者中mGluR 5可用性降低的状态是否在戒断期间（脱毒后2个月和6个月）正常化，以及初始mGluR 5成像参数是否可以预测个体复发。研究方法：对16名最近脱毒的酒精依赖患者（基线条件）、脱毒后2个月（n = 10）和脱毒后6个月（n = 8）进行F-18-FPEB扫描;包括32名年龄和性别匹配的对照进行比较。mGluR 5可用性通过F-18-FPEB总分布体积使用逐体素分析和感兴趣体积分析来量化。在随访期间，使用酒精欲望问卷评估渴望，使用时间轴随访方法评估酒精消耗，并通过头发乙基葡萄糖醛酸苷分析进行监测。结果如下：在戒酒期间，酒精依赖患者表现出持续恢复mGluR 5可用性在皮质和皮质下区域与基线相比，高达对照组中观察到的水平，6个月后，在大多数地区，除了海马，丘脑核。在6个月随访期内复发的患者中，基线时观察到较高的纹状体-苍白球mGluR 5可用性（+25.1%）。此外，纹状体mGluR 5正常化到对照水平与减少的渴望有关（“饮酒的欲望和意图”和“负强化”; r = 0.72-0.94）。结论：酒精依赖患者大脑mGluR 5可用性降低在戒酒期间恢复，并与渴望减少有关。酒精依赖者纹状体mGluR 5可用性较高可能与长期复发有关。
Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular, cerebral metabotropic glutamate receptor 5 (mGluR5). F-18-3-fluoro-5-[(pyridin3-yl)ethynyl]benzonitrile (F-18-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: F-18-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 F-18-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.