Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan, USA.
Anesthesiology. 2011 Oct;115(4):743-53. doi: 10.1097/ALN.0b013e31822e9f85.
Buprenorphine, a partial μ-opioid receptor agonist and κ-opioid receptor antagonist, is an effective analgesic. The effects of buprenorphine on sleep have not been well characterized. This study tested the hypothesis that an antinociceptive dose of buprenorphine decreases sleep and decreases adenosine concentrations in regions of the basal forebrain and pontine brainstem that regulate sleep.
Male Sprague Dawley rats were implanted with intravenous catheters and electrodes for recording states of wakefulness and sleep. Buprenorphine (1 mg/kg) was administered systemically via an indwelling catheter and sleep-wake states were recorded for 24 h. In additional rats, buprenorphine was delivered by microdialysis to the pontine reticular formation and substantia innominata of the basal forebrain while adenosine was simultaneously measured.
An antinociceptive dose of buprenorphine caused a significant increase in wakefulness (25.2%) and a decrease in nonrapid eye movement sleep (-22.1%) and rapid eye movement sleep (-3.1%). Buprenorphine also increased electroencephalographic delta power during nonrapid eye movement sleep. Coadministration of the sedative-hypnotic eszopiclone diminished the buprenorphine-induced decrease in sleep. Dialysis delivery of buprenorphine significantly decreased adenosine concentrations in the pontine reticular formation (-14.6%) and substantia innominata (-36.7%). Intravenous administration of buprenorphine significantly decreased (-20%) adenosine in the substantia innominata.
Buprenorphine significantly increased time spent awake, decreased nonrapid eye movement sleep, and increased latency to sleep onset. These disruptions in sleep architecture were mitigated by coadministration of the nonbenzodiazepine sedative-hypnotic eszopiclone. The buprenorphine-induced decrease in adenosine concentrations in basal forebrain and pontine reticular formation is consistent with the interpretation that decreasing adenosine in sleep-regulating brain regions is one mechanism by which opioids disrupt sleep.
丁丙诺啡是一种部分μ-阿片受体激动剂和κ-阿片受体拮抗剂，具有有效的镇痛作用。丁丙诺啡对睡眠的影响尚未得到很好的描述。本研究旨在验证以下假设，即丁丙诺啡的镇痛剂量会减少睡眠，并降低调节睡眠的基底前脑和脑桥脑干部位的腺苷浓度。
雄性 Sprague Dawley 大鼠植入静脉导管和电极，用于记录清醒和睡眠状态。通过留置导管系统给予丁丙诺啡（1mg/kg），并记录 24 小时的睡眠-觉醒状态。在其他大鼠中，通过微透析将丁丙诺啡递送至脑桥网状结构和基底前脑的无名质，同时测量腺苷。
镇痛剂量的丁丙诺啡可显著增加觉醒时间（25.2%），减少非快速眼动睡眠（-22.1%）和快速眼动睡眠（-3.1%）。丁丙诺啡还增加了非快速眼动睡眠期间的脑电图 δ 功率。镇静催眠药右佐匹克隆的共同给药可减轻丁丙诺啡引起的睡眠减少。丁丙诺啡的透液传递显著降低了脑桥网状结构（-14.6%）和无名质（-36.7%）中的腺苷浓度。静脉内给予丁丙诺啡可显著降低无名质中的腺苷（-20%）。
丁丙诺啡显著增加清醒时间，减少非快速眼动睡眠，增加入睡潜伏期。这些睡眠结构的破坏通过共同给予非苯二氮䓬类镇静催眠药右佐匹克隆得到缓解。丁丙诺啡降低基底前脑和脑桥网状结构中腺苷浓度，这与阿片类药物破坏睡眠的一种机制是通过降低睡眠调节脑区中的腺苷浓度的解释一致。
