Opioid use disorder (OUD) has been associated with the emergence of sleep disturbances. Although effective treatments for OUD exist, evidence suggests that these treatments also may be associated with sleep impairment. The extent to which these effects are an effect of OUD treatment or a result of chronic opioid use remains unknown. We investigated the acute effects of methadone, buprenorphine, and naltrexone on actigraphy-based sleep-like parameters in non-opioid-dependent male rhesus monkeys (Macaca mulatta, n = 5). Subjects were fitted with actigraphy monitors attached to primate collars to measure sleep-like parameters. Actigraphy recordings were conducted under baseline conditions, or following acute injections of vehicle, methadone (0.03–1.0 mg/kg, i.m.), buprenorphine (0.01–1.0 mg/kg, i.m.), or naltrexone (0.03–1.0 mg/kg, i.m.) in the morning (4 h after “lights on”) or in the evening (1.5 h before “lights off”). Morning and evening treatments with methadone or buprenorphine significantly increased sleep latency and decreased sleep efficiency. The effects of buprenorphine on sleep-like measures resulted in a biphasic dose–response function, with the highest doses not disrupting actigraphy-based sleep. Buprenorphine induced a much more robust increase in sleep latency and decrease in sleep efficiency compared to methadone, particularly with evening administration, and detrimental effects of buprenorphine on sleep-like measures were observed up to 25.5 h after drug injection. Treatment with naltrexone, on the other hand, significantly improved sleep-like measures, with evening treatments improving both sleep latency and sleep efficiency. The currently available pharmacotherapies for OUD significantly alter sleep-like parameters in non-opioid-dependent monkeys, and opioid-dependent mechanisms may play a significant role in sleep-wake regulation.

阿片类药物使用障碍（OUD）与睡眠障碍的出现有关。尽管存在 OUD 的有效治疗方法，但有证据表明这些治疗也可能与睡眠障碍有关。这些影响在多大程度上是 OUD 治疗的影响或长期使用阿片类药物的结果仍然未知。我们研究了美沙酮、丁丙诺啡和纳曲酮对非阿片类药物依赖性雄性恒河猴（猕猴，n = 5）基于体动记录仪的睡眠样参数的急性影响。受试者在灵长类动物项圈上安装了体动监测仪，以测量睡眠样参数。体动记录仪记录是在基线条件下进行的，或者在急性注射赋形剂、美沙酮（0.03-1.0 mg/kg，肌肉注射）、丁丙诺啡（0.01-1.0 mg/kg，肌肉注射）或纳曲酮（0.03-1.0 mg/kg，肌肉注射）后进行。 ）在早上（“开灯”后 4 小时）或晚上（“关灯”前 1.5 小时）。早晚使用美沙酮或丁丙诺啡治疗会显着延长睡眠潜伏期并降低睡眠效率。丁丙诺啡对类睡眠测量的影响导致双相剂量反应功能，最高剂量不会扰乱基于体动记录的睡眠。与美沙酮相比，丁丙诺啡会导致睡眠潜伏期的增加和睡眠效率的下降，特别是在晚上给药时，并且在注射药物后长达 25.5 小时内观察到丁丙诺啡对类睡眠指标的有害影响。另一方面，纳曲酮治疗显着改善了类睡眠指标，夜间治疗可改善睡眠潜伏期和睡眠效率。 目前可用的 OUD 药物疗法显着改变非阿片类药物依赖性猴子的睡眠样参数，阿片类药物依赖性机制可能在睡眠-觉醒调节中发挥重要作用。