Buprenorphine Disrupts Sleep and Decreases Adenosine Concentrations in Sleep-regulating Brain Regions of Sprague Dawley Rat
Buprenorphine Disrupts Sleep and Decreases Adenosine Concentrations in Sleep-regulating Brain Regions of Sprague Dawley Rat
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DOI：
10.1097/aln.0b013e31822e9f85
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发表时间：
2011-10-01
期刊：
影响因子：
8.8
通讯作者：
Lydic, Ralph
中科院分区：
文献类型：
--
作者：
Gauthier, Elizabeth A.;Guzick, Sarah E.;Lydic, Ralph
背景：丁丙诺啡是一种μ阿片受体部分激动剂和κ阿片受体拮抗剂，是一种有效的镇痛药。丁丙诺啡对睡眠的影响尚未得到很好的表征。本研究测试的假设，一个抗伤害剂量的丁丙诺啡减少睡眠和降低腺苷浓度的区域的基底前脑和脑桥脑干，调节sleep.Methods：雄性Sprague道利大鼠植入静脉导管和电极记录状态的觉醒和睡眠。通过留置导管全身给予丁丙诺啡（1 mg/kg），记录24 h的睡眠-觉醒状态。在另外的大鼠，丁丙诺啡通过微透析传递到脑桥网状结构和无名质的基底前脑，而腺苷是同时measured.Results：丁丙诺啡的抗伤害剂量引起清醒（25.2%）和减少非快速眼动睡眠（-22.1%）和快速眼动睡眠（-3.1%）的显着增加。丁丙诺啡也增加了非快速眼动睡眠期间的脑电图δ功率。同时给予镇静催眠药右佐匹克隆可减少丁丙诺啡诱导的睡眠减少。丁丙诺啡的透析输送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。静脉注射丁丙诺啡显著降低（-20%）腺苷在substitutia innominata.Conclusions：丁丙诺啡显着增加清醒时间，减少非快速眼动睡眠，并增加潜伏期入睡。这些睡眠结构的破坏通过与非苯二氮卓类镇静催眠药右佐匹克隆联合给药得以缓解。丁丙诺啡诱导的基底前脑和脑桥网状结构中腺苷浓度的降低与以下解释一致：睡眠调节脑区中腺苷的降低是阿片类药物干扰睡眠的一种机制。
Background: Buprenorphine, a partial mu-opioid receptor agonist and kappa-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.Methods: 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.Results: 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.Conclusions: 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.