title: Effects of amphetamine, diazepam and caffeine on polysomnography (EEG, EMG, EOG)-derived variables measured using telemetry in Cynomolgus monkeys.
abstract: BACKGROUND
  Medication-induced sleep disturbances are a major concern in drug development as a multitude of prescription drugs alter sleep patterns, often negatively. Polysomnography is used in clinical diagnostics but is also applicable to animal models. Rodent sleep architecture (nocturnal) differs from larger diurnal mammals, including humans, increasing the translational potential of non-rodent species to the clinic. This study aimed to characterize the response to pharmacological agents known to affect sleep structure and EEG activity in a non-human primate (Macaca fascicularis) using telemetry-based polysomnography.
  
  
  METHODS
  Animals were instrumented with telemetry transmitters for continuous electroencephalogram (EEG), electro-oculogram (EOG) and electromyogram (EMG) monitoring combined with video. EEG, EMG and EOG were monitored for 12 to 24h to establish baseline values, followed by administration of pharmacological agents (saline, d-amphetamine, diazepam or caffeine).
  
  
  RESULTS
  Amphetamine (0.3 and 1mg/kg, by oral administration (PO)) significantly reduced total sleep time, including the duration of both non-rapid eye movement [NREM] sleep and REM sleep. It also decreased EEG activity in low frequencies (i.e., 4-6Hz) during wakefulness. Diazepam (2mg/kg, PO) did not significantly alter sleep duration, but importantly reduced EEG activity in low frequencies (approximately 2-12Hz) during wakefulness, NREM and REM sleep. Finally, caffeine (10 and 30mg/kg, PO) decreased both NREM and REM sleep duration. In addition, spectral analysis revealed important decreases in low frequency activity (i.e., 1-8Hz) during wakefulness with a parallel increase in high frequency activity (i.e., 20-50Hz) during NREM sleep.
  
  
  CONCLUSIONS
  As these observations are similar to previously reported pharmacological effects in humans, results support that EEG, EOG and EMG monitoring by telemetry in Cynomolgus monkeys represents a useful non-clinical model to investigate and quantify drug-induced sleep disturbances.
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3; Faculty of Veterinary Medicine, University of Montreal, P.O. box 5000, St-Hyacinthe, QC, Canada, J2S 7C6. Electronic address: authiers@ca.citoxlab.com.
authors.forename: Simon
authors.initials: S
authors.lastname: Authier
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3; Faculty of Veterinary Medicine, University of Montreal, P.O. box 5000, St-Hyacinthe, QC, Canada, J2S 7C6.
authors.forename: Leanne
authors.initials: L
authors.lastname: Bassett
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3.
authors.forename: Mylene
authors.initials: M
authors.lastname: Pouliot
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Coeur de Montréal, Montreal, QC, Canada, H4J 1C5.
authors.forename: Adeline
authors.initials: A
authors.lastname: Rachalski
authors.affiliation: Faculty of Veterinary Medicine, University of Montreal, P.O. box 5000, St-Hyacinthe, QC, Canada, J2S 7C6.
authors.forename: Eric
authors.initials: E
authors.lastname: Troncy
authors.affiliation: CIToxLAB North America, 445 Armand Frappier, Laval, QC, Canada, H7V 4B3.
authors.forename: Dominique
authors.initials: D
authors.lastname: Paquette
authors.affiliation: Center for Advanced Research in Sleep Medicine and Research Center, Hôpital du Sacré-Coeur de Montréal, Montreal, QC, Canada, H4J 1C5; Department of Neuroscience, Université de Montréal, Montreal, QC, Canada, H3C 3J7.
authors.forename: Valérie
authors.initials: V
authors.lastname: Mongrain
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology*; D004569:Electroencephalography / Q000187:drug effects* / Q000379:methods; D004576:Electromyography / Q000187:drug effects* / Q000379:methods; D004585:Electrooculography / Q000187:drug effects* / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal; D017286:Polysomnography / Q000187:drug effects*; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects; D013686:Telemetry / Q000379:methods; D014851:Wakefulness / Q000187:drug effects
chemical_list: D002110:Caffeine; D000661:Amphetamine; D003975:Diazepam
keywords: Animal model; EEG spectral analysis; Macaca fascicularis; Pharmacology; Sleep stages; Telemetry