title: Gamma-aminobutyric acid type A receptor β3 subunit forebrain-specific knockout mice are resistant to the amnestic effect of isoflurane.
abstract: BACKGROUND
  β3 containing γ-aminobutyric acid type A receptors (GABA(A)-Rs) mediate behavioral end points of IV anesthetics such as immobility and hypnosis. A knockout mouse with targeted forebrain deletion of the β3 subunit of the GABA(A)-R shows reduced sensitivity to the hypnotic effect of etomidate, as measured by the loss of righting reflex. The end points of amnesia and immobility produced by an inhaled anesthetic have yet to be evaluated in this conditional knockout.
  
  
  METHODS
  We assessed forebrain selective β3 conditional knockout mice and their littermate controls for conditional fear to evaluate amnesia and MAC, the minimum alveolar concentration of inhaled anesthetic necessary to produce immobility in response to noxious stimulation, to assess immobility. Suppression of conditional fear was assessed for etomidate and isoflurane, and MAC was assessed for isoflurane.
  
  
  RESULTS
  Etomidate equally suppressed conditional fear for both genotypes. The knockout showed resistance to the suppression of conditional fear produced by isoflurane in comparison with control littermates. Controls and knockouts did not differ in isoflurane MAC values.
  
  
  CONCLUSIONS
  These results suggest that β3 containing GABA(A)-Rs in the forebrain contribute to hippocampal-dependent memory suppressed by isoflurane, but not etomidate.
authors.affiliation: Department of Anesthesia, S-455, University of California San Francisco, San Francisco, CA 94143-0464, USA. vinutarau@yahoo.com
authors.forename: Vinuta
authors.initials: V
authors.lastname: Rau
authors.forename: Irene
authors.initials: I
authors.lastname: Oh
authors.forename: Mark
authors.initials: M
authors.lastname: Liao
authors.forename: Christina
authors.initials: C
authors.lastname: Bodarky
authors.forename: Michael S
authors.initials: MS
authors.lastname: Fanselow
authors.forename: Gregg E
authors.initials: GE
authors.lastname: Homanics
authors.forename: James M
authors.initials: JM
authors.lastname: Sonner
authors.forename: Edmond I
authors.initials: EI
authors.lastname: Eger
mesh_terms: D000647:Amnesia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000523:psychology; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000633:toxicity*; D018686:Anesthetics, Intravenous / Q000633:toxicity; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003213:Conditioning, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005045:Etomidate / Q000633:toxicity; D005239:Fear / Q000187:drug effects; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007530:Isoflurane / Q000633:toxicity*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D017711:Nonlinear Dynamics; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000172:deficiency* / Q000235:genetics
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; C546270:Gabrb3 protein, mouse; D011963:Receptors, GABA-A; D007530:Isoflurane; D005045:Etomidate