title: Spontaneous hyperactivity in mutant mice lacking the NMDA receptor GluRepsilon1 subunit is aggravated during exposure to 0.1 MAC sevoflurane and is preserved after emergence from sevoflurane anaesthesia.
abstract: OBJECTIVE
  Patients who awake from sevoflurane anaesthesia with symptoms of agitation may have some underlying functional substrate that is sensitive to the low concentrations of anaesthetic encountered during emergence. One candidate for such a substrate could be neurocircuitry implied in the pathophysiology of both agitation and movement disorders with hyperactivity. We postulated that hyperactive animals would show a further increase in activity in the presence of low concentrations of volatile anaesthetics, such as sevoflurane.
  
  
  METHODS
  To confirm our hypothesis, we examined the effects of two subanaesthetic concentrations of sevoflurane, isoflurane and halothane (0.1 and 0.2 MAC (minimum alveolar concentration)) on spontaneous activity in N-methyl-d-aspartate receptor GluRepsilon1 subunit knockout mice exhibiting locomotor hyperactivity in a novel environment and compared these results with those for wild-type controls. We also compared the effects of anaesthetic concentrations of sevoflurane (1.2 MAC) on mice activity during postanaesthesia recovery.
  
  
  RESULTS
  Out of the three anaesthetics used, only sevoflurane administered at 0.1 MAC caused a significantly different response between the two experimental groups. Exposure to this subanaesthetic concentration of sevoflurane reduced the activity of wild-type mice, whereas mutant animals showed a further increase in hyperactivity. The effects of 1.2 MAC sevoflurane anaesthesia on mice activity during postanaesthesia recovery also differed significantly between the two genotypes. Exposure to anaesthetic concentrations of sevoflurane had a sedative effect on wild-type mice, whereas mutant mice preserved their high levels of activity upon emergence from the anaesthesia.
  
  
  CONCLUSIONS
  The presence of an inherent anomaly in mutant mice that becomes more manifest during exposure to 0.1 MAC sevoflurane and is still present after the emergence from sevoflurane anaesthesia suggests the presence of and necessitates a search for some putative substrate that may, by analogy, underlie emergence agitation in the clinical setting.
authors.affiliation: Niigata University Graduate School of Medical and Dental Sciences, Division of Anesthesiology, Niigata, Japan. abpetr@med.niigata-u.ac.jp
authors.forename: A B
authors.initials: AB
authors.lastname: Petrenko
authors.forename: T
authors.initials: T
authors.lastname: Kohno
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: K
authors.initials: K
authors.lastname: Sakimura
authors.forename: H
authors.initials: H
authors.lastname: Baba
mesh_terms: D017109:Akathisia, Drug-Induced / Q000209:etiology; D000762:Anesthesia Recovery Period; D000769:Anesthesia, Inhalation / Q000009:adverse effects*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D006221:Halothane / Q000008:administration & dosage / Q000009:adverse effects; D007530:Isoflurane / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D009154:Mutation; D011595:Psychomotor Agitation / Q000209:etiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000235:genetics*; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000077149:Sevoflurane; D007530:Isoflurane; D006221:Halothane