DMSO potentiates the suppressive effect of dronabinol on sleep apnea and REM sleep in rats.

Michael W Calik, David W Carley
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Abstract

Introduction: Dimethyl sulfoxide (DMSO) is an amphipathic molecule with innate biological activity that also is used to dissolve both polar and nonpolar compounds in preclinical and clinical studies. Recent investigations of dronabinol, a cannabinoid, dissolved in DMSO demonstrated decreased sleep apnea frequency and time spent in REM sleep in rats. Here, we tested the effects of dronabinol dissolved in 25% DMSO diluted in phosphate-buffered saline (PBS) to rule out potentiating effects of DMSO.

Methods: Sprague-Dawley rats were anesthetized and implanted with bilateral stainless steel screws into the skull for electroencephalogram recording and bilateral wire electrodes into the nuchal muscles for electromyogram recording. Each animal was recorded by polysomnography. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections separated by three days: vehicle (25% DMSO/PBS); vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol (CB1/CB2 agonist); dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonists. Sleep was manually scored into NREM and REM stages, and sleep apneas were quantified.

Results: Dronabinol dissolved in 25% DMSO did not suppress sleep apneas or modify sleep efficiency compared to vehicle controls, in contrast to previously published results. However, dronabinol did suppress REM sleep, which is in line with previously published results.

Conclusions: Dronabinol in 25% DMSO partially potentiated dronabinol's effects, suggesting a concomitant biological effect of DMSO on breathing during sleep.

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DMSO增强了屈大麻酚对大鼠睡眠呼吸暂停和快速眼动睡眠的抑制作用。
简介:二甲基亚砜(DMSO)是一种具有先天生物活性的两亲性分子,在临床前和临床研究中也被用于溶解极性和非极性化合物。最近对溶解在DMSO中的大麻素屈大麻酚的研究表明,大鼠睡眠呼吸暂停频率和快速眼动睡眠时间减少。在这里,我们测试了溶解在25%的DMSO中溶解在磷酸盐缓冲盐水(PBS)中的效应,以排除DMSO的增强效应。方法:Sprague-Dawley大鼠麻醉后,双侧不锈钢螺钉置入颅骨内记录脑电图,双侧丝电极置入颈肌内记录肌电图。采用多导睡眠描记法对每只动物进行记录。该研究采用全巢式重复测量交叉设计,每只大鼠在8次腹腔注射后分别进行记录,每次注射间隔3天:载药(25% DMSO/PBS);载体和CB1拮抗剂(am251);载体和CB2拮抗剂(am630);CB1/CB2拮抗剂;屈大麻酚(CB1/CB2激动剂);屈大麻酚和CB1拮抗剂;屈大麻酚和CB2拮抗剂;屈大麻酚和CB1/CB2拮抗剂。人工将睡眠分为非快速眼动期和快速眼动期,并对睡眠呼吸暂停进行量化。结果:与先前发表的结果相比,溶在25% DMSO中的曲大麻酚没有抑制睡眠呼吸暂停或改变睡眠效率。然而,曲大麻酚确实抑制了快速眼动睡眠,这与之前发表的结果一致。结论:25% DMSO中的屈大麻酚部分增强了屈大麻酚的作用,提示DMSO对睡眠呼吸的伴随生物学效应。
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