title: Sleep and general anesthesia.
abstract: OBJECTIVE
  The mechanisms through which general anesthetics cause reversible loss of consciousness are characterized poorly. In this review, we examine the evidence that anesthetic-induced loss of consciousness may be caused by actions on the neuronal pathways that produce natural sleep.
  
  
  RESULTS
  It is clear that many general anesthetics produce effects in the brain (detected on electroencephalogram recordings) that are similar to those seen during non-rapid eye movement non-(REM) sleep. Gamma aminobutyric acid (GABA)ergic hypnogenic neurons are thought to be critical for generating non-REM sleep through their inhibitory projections to wake-active regions of the brain. The postsynaptic GABA(A) receptor is a major molecular target of many anesthetics and thus may be a point of convergence between natural sleep and anesthesia. Furthermore, we also present growing evidence in this review that modulating wake-active neurotransmitter (e.g., acetylcholine, histamine) release can impact on anesthesia, supporting the idea that this point of convergence is at the level of the brain arousal systems.
  
  
  CONCLUSIONS
  While it is clear that general anesthetics can have effects at various points in the sleep-wake circuitry, it remains to be seen which points are true anesthetic targets. It will be challenging to separate non-specific effects on baseline arousal from a causal mechanism. Sophisticated experimental approaches are necessary to address basic mechanisms of sleep and anesthesia and should advance our understanding in both of these fields.
authors.affiliation: Biophysics Section, Blackett Laboratory, Division of Cell and Molecular Biology, Imperial College, South Kensington, London, SW7 2AZ, UK. n.franks@imperial.ac.uk
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Franks
authors.forename: Anna Y
authors.initials: AY
authors.lastname: Zecharia
mesh_terms: D018681:Anesthetics, General / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004569:Electroencephalography; D006801:Humans; D009434:Neural Pathways / Q000187:drug effects* / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages / Q000502:physiology
chemical_list: D018681:Anesthetics, General