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Cannabinoid type 1 and type 2 receptor antagonists prevent attenuation of serotonin-induced reflex apneas by dronabinol in Sprague-Dawley rats.
PLoS One. 2014; 9(10):e111412.Plos

Abstract

The prevalence of obstructive sleep apnea (OSA) in Americans is 9% and increasing. Increased afferent vagal activation may predispose to OSA by reducing upper airway muscle activation/patency and disrupting respiratory rhythmogenesis. Vagal afferent neurons are inhibited by cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors in animal models of vagally-mediated behaviors. Injections of dronabinol, a non-selective CB1/CB2 receptor agonist, into the nodose ganglia reduced serotonin (5-HT)-induced reflex apneas. It is unknown what role CB1 and/or CB2 receptors play in reflex apnea. Here, to determine the independent and combined effects of activating CB1 and/or CB2 receptors on dronabinol's attenuating effect, rats were pre-treated with CB1 (AM251) and/or CB2 (AM630) receptor antagonists. Adult male Sprague-Dawley rats were anesthetized, instrumented with bilateral electrodes to monitor genioglossus electromyogram (EMGgg) and a piezoelectric strain gauge to monitor respiratory pattern. Following intraperitoneal treatment with AM251 and/or AM630, or with vehicle, serotonin was intravenously infused into a femoral vein to induce reflex apnea. After baseline recordings, the nodose ganglia were exposed and 5-HT-induced reflex apneas were again recorded to confirm that the nerves remained functionally intact. Dronabinol was injected into each nodose ganglion and 5-HT infusion was repeated. Prior to dronabinol injection, there were no significant differences in 5-HT-induced reflex apneas or phasic and tonic EMGgg before or after surgery in the CB1, CB2, combined CB1/CB2 antagonist, and vehicle groups. In the vehicle group, dronabinol injections reduced 5-HT-induced reflex apnea duration. In contrast, dronabinol injections into nodose ganglia of the CB1, CB2, and combined CB1/CB2 groups did not attenuate 5-HT-induced reflex apnea duration. However, the CB1 and CB2 antagonists had no effect on dronabinol's ability to increase phasic EMGgg. These findings underscore the therapeutic potential of dronabinol in the treatment of OSA and implicate participation of both cannabinoid receptors in dronabinol's apnea suppression effect.

Authors+Show Affiliations

Center for Narcolepsy, Sleep and Health Research, University of Illinois at Chicago, Chicago, Illinois, United States of America; Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago, Illinois, United States of America.Center for Narcolepsy, Sleep and Health Research, University of Illinois at Chicago, Chicago, Illinois, United States of America; Department of Biobehavioral Health Science, University of Illinois at Chicago, Chicago, Illinois, United States of America; Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25350456

Citation

Calik, Michael W., and David W. Carley. "Cannabinoid Type 1 and Type 2 Receptor Antagonists Prevent Attenuation of Serotonin-induced Reflex Apneas By Dronabinol in Sprague-Dawley Rats." PloS One, vol. 9, no. 10, 2014, pp. e111412.
Calik MW, Carley DW. Cannabinoid type 1 and type 2 receptor antagonists prevent attenuation of serotonin-induced reflex apneas by dronabinol in Sprague-Dawley rats. PLoS One. 2014;9(10):e111412.
Calik, M. W., & Carley, D. W. (2014). Cannabinoid type 1 and type 2 receptor antagonists prevent attenuation of serotonin-induced reflex apneas by dronabinol in Sprague-Dawley rats. PloS One, 9(10), e111412. https://doi.org/10.1371/journal.pone.0111412
Calik MW, Carley DW. Cannabinoid Type 1 and Type 2 Receptor Antagonists Prevent Attenuation of Serotonin-induced Reflex Apneas By Dronabinol in Sprague-Dawley Rats. PLoS One. 2014;9(10):e111412. PubMed PMID: 25350456.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cannabinoid type 1 and type 2 receptor antagonists prevent attenuation of serotonin-induced reflex apneas by dronabinol in Sprague-Dawley rats. AU - Calik,Michael W, AU - Carley,David W, Y1 - 2014/10/28/ PY - 2014/08/01/received PY - 2014/10/02/accepted PY - 2014/10/29/entrez PY - 2014/10/29/pubmed PY - 2016/1/9/medline SP - e111412 EP - e111412 JF - PloS one JO - PLoS One VL - 9 IS - 10 N2 - The prevalence of obstructive sleep apnea (OSA) in Americans is 9% and increasing. Increased afferent vagal activation may predispose to OSA by reducing upper airway muscle activation/patency and disrupting respiratory rhythmogenesis. Vagal afferent neurons are inhibited by cannabinoid type 1 (CB1) or cannabinoid type 2 (CB2) receptors in animal models of vagally-mediated behaviors. Injections of dronabinol, a non-selective CB1/CB2 receptor agonist, into the nodose ganglia reduced serotonin (5-HT)-induced reflex apneas. It is unknown what role CB1 and/or CB2 receptors play in reflex apnea. Here, to determine the independent and combined effects of activating CB1 and/or CB2 receptors on dronabinol's attenuating effect, rats were pre-treated with CB1 (AM251) and/or CB2 (AM630) receptor antagonists. Adult male Sprague-Dawley rats were anesthetized, instrumented with bilateral electrodes to monitor genioglossus electromyogram (EMGgg) and a piezoelectric strain gauge to monitor respiratory pattern. Following intraperitoneal treatment with AM251 and/or AM630, or with vehicle, serotonin was intravenously infused into a femoral vein to induce reflex apnea. After baseline recordings, the nodose ganglia were exposed and 5-HT-induced reflex apneas were again recorded to confirm that the nerves remained functionally intact. Dronabinol was injected into each nodose ganglion and 5-HT infusion was repeated. Prior to dronabinol injection, there were no significant differences in 5-HT-induced reflex apneas or phasic and tonic EMGgg before or after surgery in the CB1, CB2, combined CB1/CB2 antagonist, and vehicle groups. In the vehicle group, dronabinol injections reduced 5-HT-induced reflex apnea duration. In contrast, dronabinol injections into nodose ganglia of the CB1, CB2, and combined CB1/CB2 groups did not attenuate 5-HT-induced reflex apnea duration. However, the CB1 and CB2 antagonists had no effect on dronabinol's ability to increase phasic EMGgg. These findings underscore the therapeutic potential of dronabinol in the treatment of OSA and implicate participation of both cannabinoid receptors in dronabinol's apnea suppression effect. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25350456/Cannabinoid_type_1_and_type_2_receptor_antagonists_prevent_attenuation_of_serotonin_induced_reflex_apneas_by_dronabinol_in_Sprague_Dawley_rats_ L2 - https://dx.plos.org/10.1371/journal.pone.0111412 DB - PRIME DP - Unbound Medicine ER -