The Subjective Response to Nitrous Oxide is a Potential Pharmaco-Endophenotype for Alcohol Use Disorder: A Preliminary Study with Heavy Drinkers.
The Subjective Response to Nitrous Oxide is a Potential Pharmaco-Endophenotype for Alcohol Use Disorder: A Preliminary Study with Heavy Drinkers.
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DOI：
10.1093/ijnp/pyw063
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发表时间：
2017-04-01
期刊：
影响因子：
--
通讯作者：
Kamboj SK
中科院分区：
文献类型：
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作者：
Walsh K;Das RK;Kamboj SK
有酒精问题家族史的健康人对酒精的主观反应模式与受影响的先证者相似。对氯胺酮的研究表明，N-甲基-D-天冬氨酸受体（NMDAR）的上调是这些作用的基础，并指出了反映酒精使用障碍风险增加的药理学反应性内表型。主观刺激和镇静作用进行了评估之前和期间的一氧化二氮（N2 O; 50%）吸入重度饮酒者谁是健康的。有酒精使用障碍家族史的受试者（n = 23）与无此类家族风险的受试者（n = 37）在吸入N2 O期间通过增强的刺激-镇静比进行区分。根据家族风险，N2 O的主观效应模式与先前在氯胺酮中观察到的模式非常相似，支持共同的NMDAR介导的作用机制的想法。N2 O可能被证明是氯胺酮的安全和可获得的替代品，用于探测神经精神疾病中的遗传性NMDAR失调。
Healthy people with a family history of alcohol problems show a pattern of subjective responses to alcohol that resemble those of affected probands. Studies on ketamine suggest that up-regulation of N-methyl-D-aspartate receptors (NMDARs) underlies these effects, and point to a pharmacologically-responsive endophenotype reflecting enhanced risk for alcohol-use disorders. Subjective stimulant and sedative effects were assessed before and during nitrous oxide (N2O; 50%) inhalation in heavy drinkers who were otherwise healthy. Participants with an ostensible family history of alcohol-use disorders (n = 23) were distinguishable from those without such familial risk (n = 37) by an enhanced stimulation-to-sedation ratio during N2O inhalation. The pattern of subjective effects of N2O according to familial risk is remarkably similar to that previously seen with ketamine, supporting the idea of a common, NMDAR-mediated mechanism of action. N2O may prove to be a safe and accessible alternative to ketamine for probing heritable NMDAR dysregulation in neuropsychiatric disorders.