title: Intracerebroventricular injections of dronabinol, a cannabinoid receptor agonist, does not attenuate serotonin-induced apnea in Sprague-Dawley rats.
abstract: BACKGROUND
  Evidence suggests that vagal nerve activity may play a role in sleep apnea induction. In anesthetized rats, dronabinol, a cannabinoid (CB) receptor agonist, injected into the nodose ganglia attenuates reflex apnea and increases genioglossus activity, and reflex apnea attenuation is blocked by systemic pre-treatment with cannabinoid type 1 and/or type 2 receptor antagonists. However, it is unclear whether dronabinol has similar effects in the central nervous system; CB receptors are widely distributed in the brain, especially on neuronal circuitry important for respiration and upper airway activation. Here, we examine the effects of intracerebroventricular (ICV) injection of dronabinol on serotonin (5-HT)-induced apnea.
  
  
  METHODS
  Adult male Sprague-Dawley rats were anesthetized and instrumented with bilateral electrodes to monitor genioglossi EMG and with a piezoelectric strain gauge to monitor respiratory pattern. Serotonin was intravenously infused into a femoral vein to induce reflex apnea. After baseline recordings, rats were placed in a stereotaxic apparatus. A unilateral osteotomy was made to allow access for injection to the right lateral ventricle, and the dura were carefully removed. Dronabinol (100, 10, 1, or 0.1 μg/3 μl DMSO) or control (3 μl DMSO) was injected into the right lateral ventricle and 5-HT infusion was repeated. Data (mean ± SEM) were analyzed using a mixed model analysis with a repeated/fixed measure.
  
  
  RESULTS
  There was no main effect in 5-HT-induced apnea or breath duration, or in breath instability, between ICV dronabinol injected and ICV vehicle control injected groups. Moreover, there was no main effect in phasic or tonic genioglossus activity between ICV dronabinol injected and ICV vehicle control injected groups.
  
  
  CONCLUSIONS
  Our data show that ICV injection of dronabinol did not decrease 5-HT-induced apneas, and did not increase genioglossus activity. This in contrast to published results of dronabinol's effect on apnea via the vagus nerve. Our results suggest that the effects of dronabinol on reflex apneas are peripherally mediated via suppression of vagal nerve activity.
authors.affiliation: Center for Narcolepsy, Sleep and Health Research, University of Illinois at Chicago, 845 South Damen Avenue (M/C 802), Chicago, IL, 60612, USA. mcalik@uic.edu.|Department of Biobehavioral Health Science, University of Illinois at Chicago, 845 South Damen Avenue (M/C 802), Chicago, IL, 60612, USA. mcalik@uic.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Calik
authors.affiliation: Center for Narcolepsy, Sleep and Health Research, University of Illinois at Chicago, 845 South Damen Avenue (M/C 802), Chicago, IL, 60612, USA.|Department of Biobehavioral Health Science, University of Illinois at Chicago, 845 South Damen Avenue (M/C 802), Chicago, IL, 60612, USA.|Department of Medicine, University of Illinois at Chicago, 1853 West Polk Street (M/C 784), Chicago, IL, 60612, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Carley
mesh_terms: D000818:Animals; D001049:Apnea / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D013759:Dronabinol / Q000008:administration & dosage* / Q000494:pharmacology; D004576:Electromyography; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000008:administration & dosage*
chemical_list: D063386:Cannabinoid Receptor Agonists; D012701:Serotonin; D013759:Dronabinol
keywords: Cannabinoids; Dronabinol; Intracerebroventricular injection; Obstructive sleep apnea; Reflex apnea; Serotonin