Nature. 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 Dronabinols effects on apneas were dependent on CB1 receptor activation, while dronabinols effects on REM sleep were CB receptor-independent. = 22; ~275 g) purchased from Harlan Laboratories GKT137831 (Indianapolis, IN) were initially housed in duplicate, maintained on a 12:12 hour light:dark cycle at 22 0.5C, and allowed ad libitum access to food and water. After surgery, rats were housed singly to prevent loss of headsets. All animal procedures and protocols were approved by the Institutional Animal Care and Use Committee of the University of Illinois at Chicago. Surgical Procedures Implantation of polygraphic headsets has been described before.1,20 Rats were anesthetized (ketamine:xylazine 100:10 mg/kg; buprenorphine 0.1 mg/kg), stereotaxically immobilized, and implanted with electroencephalographic (EEG) screw electrodes bilaterally threaded into the frontal and parietal bones. Electromyographic (EMG) wire electrodes were implanted in the dorsal nuchal musculature and tunneled subcutaneously to the skull. EEG and EMG leads were soldered to a miniature plastic connector plug (i.e. headset) and affixed to the skull acrylic dental cement. Scalp wounds were closed with Vetbond Tissue Adhesive. Rats were allowed to recover for 7 days before beginning a week of acclimation to handling and to plethysmographic recording chambers. Polysomnography and Treatment Protocol Polysomnography (PSG) procedures have been previously described.20 Rats underwent nine 6-hour PSG recording, separated by at least 3 days. All recording sessions began at 10:00 and continued until 16:00. Each rat received an IP injection (1 mL/kg total volume) at 09:45. Rats were immediately placed inside a bias-flow-ventilated (2 L/min) whole-body plethysmograph GKT137831 (PLYUNIR/U, Buxco Electronics, Wilmington, DE), where respiratory airflow was detected by changes in pressure between the main chamber and an integrated reference chamber, as previously described.9 A flexible GKT137831 cable was inserted through a narrow chimney into the main plethysmography chamber and attached to the rats headset. Rats underwent a week of acclimation to handling and to plethysmographic recording chambers, including being connected to the flexible cable. After acclimation, rats were recorded for 6 hours for one occasion prior to the first experimental session to permit adaptation to the recording system, and to assess the quality of PRKCB EEG and EMG signals. If signal quality was good, then the rats (= 8C10) underwent a repeated measures random order crossover design, such that each rat received each of 8 IP injections exactly one time in random order (i.e. any 8 of the IP injections could have been the first injection that a rat received): vehicle alone (DMSO; 1 mL); dronabinol (chemical name: (= 7.49 nM], Tocris Bioscience, Bristol, UK); AM630 (chemical came: 6-Iodo-2-methyl-1-[2-(4-morpholinyl)ethyl]-1= 31.2 nM], Tocris Bioscience); or AM 251/630 GKT137831 combination (5.0/5.0 mg/kg); or a combination injection (dronabinol and AM251 or AM630 or AM251/AM630). Respiratory signals were amplified, band-passed filtered (1 to 10 Hz; CyberAmp 380, Axon Instruments, Sunnyvale, CA), and digitized (250 samples/s; Bio-logic Sleepscan Premier, Natus, San Carlos, CA). EEG and EMG signals were amplified and band-passed filtered (0.5 to 100 Hz and 10 to 100 Hz, respectively) and digitized (250 samples/s; Bio-logic Sleepscan Premier). All data were stored to hard disk. Visual scoring was conducted by a blinded and experienced technician. Sleep stages (wake, NREM, and REM) were scored for every 30-second epoch of the 6-hour recording. Wakefulness was GKT137831 characterized by high-frequency and low-amplitude (beta/alpha waves) EEG with high EMG tone. NREM sleep was characterized low-frequency and high-amplitude (delta waves) and low EMG tone, while REM sleep was.