Sleep Homeostasis and General Anesthesia: Are Fruit Flies Well Rested after Emergence from Propofol?

• Published in: Anesthesiology (Philadelphia) 2016-02, Vol.124 (2), p.404-416
• Main Authors: Gardner, Benjamin, Strus, Ewa, Meng, Qing Cheng, Coradetti, Thomas, Naidoo, Nirinjini N, Kelz, Max B, Williams, Julie A
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Anesthesia Recovery Period; Anesthesia, General; Animals; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drosophila melanogaster; Homeostasis - drug effects; Humans; Hypnotics and Sedatives - pharmacology; Motor Activity - drug effects; Propofol - pharmacology; Proportional Hazards Models; Rest; Sleep - drug effects; Sleep Deprivation
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/ALN.0000000000000939

BACKGROUND:Shared neurophysiologic features between sleep and anesthetic-induced hypnosis indicate a potential overlap in neuronal circuitry underlying both states. Previous studies in rodents indicate that preexisting sleep debt discharges under propofol anesthesia. The authors explored the hypothesis that propofol anesthesia also dispels sleep pressure in the fruit fly. To the authors’ knowledge, this constitutes the first time propofol has been tested in the genetically tractable model, Drosophila melanogaster. METHODS:Daily sleep was measured in Drosophila by using a standard locomotor activity assay. Propofol was administered by transferring flies onto food containing various doses of propofol or equivalent concentrations of vehicle. High-performance liquid chromatography was used to measure the tissue concentrations of ingested propofol. To determine whether propofol anesthesia substitutes for natural sleep, the flies were subjected to 10-h sleep deprivation (SD), followed by 6-h propofol exposure, and monitored for subsequent sleep. RESULTS:Oral propofol treatment causes anesthesia in flies as indicated by a dose-dependent reduction in locomotor activity (n = 11 to 41 flies from each group) and increased arousal threshold (n = 79 to 137). Recovery sleep in flies fed propofol after SD was delayed until after flies had emerged from anesthesia (n = 30 to 48). SD was also associated with a significant increase in mortality in propofol-fed flies (n = 44 to 46). CONCLUSIONS:Together, these data indicate that fruit flies are effectively anesthetized by ingestion of propofol and suggest that homologous molecular and neuronal targets of propofol are conserved in Drosophila. However, behavioral measurements indicate that propofol anesthesia does not satisfy the homeostatic need for sleep and may compromise the restorative properties of sleep.