Background Nitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine. We also tested for moderation of these effects by bipolar phenotype, depressive symptoms, and impulsivity. Methods Healthy volunteers were randomly assigned to either 50% N2O (n = 40) or medical air (n = 40). Self-reported rewarding (liking and wanting), and alcohol-like effects were assessed pre-, peri- and post inhalation. Results Effect sizes for the various rewarding/alcohol-like effects of N2O were generally similar to those reported in studies of moderate-dose ketamine. Impulsivity moderated the subjective reinforcing (liking) effects of inhaled gas, while depressive symptoms moderated motivational (wanting [more]) effects. However, depression and impulsivity had opposite directional influences, such that higher impulsivity was associated with higher N2O liking, and higher depression, with lower N2O wanting. Conclusion To the extent that static (versus longitudinal) subjective rewarding effects are a reliable indicator of future problematic drug use, our findings suggests that impulsivity and depression may predispose and protect, respectively, against N2O abuse. Future studies should examine if these moderators are relevant for other NMDAR antagonists, including ketamine, and novel ketamine-like therapeutic and recreational drugs. Similarities between moderate-dose N2O and moderate-dose ketamine in the intensity of certain subjective effects suggest that N2O may, at least to some extent, serve as substitute for ketamine as a safe and easily implemented experimental tool for probing reward-related NMDAR function and dysfunction in humans.

中文翻译：

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NMDAR 拮抗剂一氧化二氮（笑气）的有益主观效果受到健康志愿者的冲动和抑郁症状的调节

背景 一氧化二氮 (N2O) 是一种具有治疗和滥用潜力的麻醉气体。由于 N2O 是一种 NMDA 受体 (NMDAR) 拮抗剂，预计其作用类似于原型 NMDAR 拮抗剂氯胺酮。在这项研究中，我们使用先前在氯胺酮研究中采用的措施检查了 N2O 的主观奖励效应。我们还测试了双相表型、抑郁症状和冲动对这些影响的调节作用。方法 健康志愿者被随机分配到 50% N2O (n = 40) 或医用空气 (n = 40)。在吸入前、吸入前后和吸入后评估自我报告的奖励（喜欢和想要）和类似酒精的效果。结果 N2O 的各种奖励/类酒精效应的效应大小通常与中等剂量氯胺酮研究中报告的效应大小相似。冲动减轻了吸入气体的主观强化（喜欢）效果，而抑郁症状减轻了动机（想要[更多]）效果。然而，抑郁和冲动具有相反的方向影响，即较高的冲动与较高的 N2O 喜好相关，较高的抑郁与较低的 N2O 需求相关。结论 就静态（相对于纵向）主观奖励效应是未来有问题的药物使用的可靠指标而言，我们的研究结果表明，冲动和抑郁可能分别诱发和保护 N2O 滥用。未来的研究应该检查这些调节剂是否与其他 NMDAR 拮抗剂相关，包括氯胺酮和新型氯胺酮样治疗和娱乐药物。