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Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats.
Sleep. 2017 09 01; 40(9)S

Abstract

Study Objectives

There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing.

Methods

Adult male 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 on multiple occasions separated by at least 3 days. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections: vehicle; vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol; dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonist.

Results

Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism.

Conclusions

Dronabinol's effects on apneas were dependent on CB1 receptor activation, while dronabinol's effects on REM sleep were CB receptor-independent.

Authors+Show Affiliations

Center for Narcolepsy, Sleep and Health Research, University of Illinois at Chicago, Chicago, IL. Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago, IL.Center for Narcolepsy, Sleep and Health Research, University of Illinois at Chicago, Chicago, IL. Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago, IL. Department of Medicine, University of Illinois at Chicago, Chicago, IL.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28934522

Citation

Calik, Michael W., and David W. Carley. "Effects of Cannabinoid Agonists and Antagonists On Sleep and Breathing in Sprague-Dawley Rats." Sleep, vol. 40, no. 9, 2017.
Calik MW, Carley DW. Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats. Sleep. 2017;40(9).
Calik, M. W., & Carley, D. W. (2017). Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats. Sleep, 40(9). https://doi.org/10.1093/sleep/zsx112
Calik MW, Carley DW. Effects of Cannabinoid Agonists and Antagonists On Sleep and Breathing in Sprague-Dawley Rats. Sleep. 2017 09 1;40(9) PubMed PMID: 28934522.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Cannabinoid Agonists and Antagonists on Sleep and Breathing in Sprague-Dawley Rats. AU - Calik,Michael W, AU - Carley,David W, PY - 2017/9/22/entrez PY - 2017/9/22/pubmed PY - 2018/4/24/medline KW - cannabinoid receptors KW - cannabinoids KW - dronabinol KW - obstructive sleep apnea KW - rat JF - Sleep JO - Sleep VL - 40 IS - 9 N2 - Study Objectives: There are no pharmacological treatments for obstructive sleep apnea syndrome, but dronabinol showed promise in a small pilot study. In anesthetized rats, dronabinol attenuates reflex apnea via activation of cannabinoid (CB) receptors located on vagal afferents; an effect blocked by cannabinoid type 1 (CB1) and/or type 2 (CB2) receptor antagonists. Here, using a natural model of central sleep apnea, we examine the effects of dronabinol, alone and in combination with selective antagonists in conscious rats chronically instrumented to stage sleep and measure cessation of breathing. Methods: Adult male 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 on multiple occasions separated by at least 3 days. The study was a fully nested, repeated measures crossover design, such that each rat was recorded following each of 8 intraperitoneal injections: vehicle; vehicle and CB1 antagonist (AM 251); vehicle and CB2 antagonist (AM 630); vehicle and CB1/CB2 antagonist; dronabinol; dronabinol and CB1 antagonist; dronabinol and CB2 antagonist; and dronabinol and CB1/CB2 antagonist. Results: Dronabinol decreased the percent time spent in rapid eye movement (REM) sleep. CB receptor antagonists did not reverse this effect. Dronabinol also decreased apneas during sleep, and this apnea suppression was reversed by CB1 or CB1/CB2 receptor antagonism. Conclusions: Dronabinol's effects on apneas were dependent on CB1 receptor activation, while dronabinol's effects on REM sleep were CB receptor-independent. SN - 1550-9109 UR - https://www.unboundmedicine.com/medline/citation/28934522/Effects_of_Cannabinoid_Agonists_and_Antagonists_on_Sleep_and_Breathing_in_Sprague_Dawley_Rats_ L2 - https://academic.oup.com/sleep/article-lookup/doi/10.1093/sleep/zsx112 DB - PRIME DP - Unbound Medicine ER -