α1 subunit-containing GABA type a receptors in forebrain contribute to the effect of inhaled anesthetics on conditioned fear

James M. Sonner, Mike Cascio, Yilei Xing, Michael S. Fanselow, Jason E. Kralic, A. Leslie Morrow, Esa R. Korpi, Steven Hardy, Brian Sloat, Edmond I. Eger, Gregg E. Homanics

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Inhaled anesthetics are believed to produce anesthesia by their actions on ion channels. Because inhaled anesthetics robustly enhance GABA A receptor (GABAA-R) responses to GABA, these receptors are considered prime targets of anesthetic action. However, the importance of GABAA-Rs and individual GABAA-R subunits to specific anesthetic-induced behavioral effects in the intact animal is unknown. We hypothesized that inhaled anesthetics produce amnesia, as assessed by loss of fear conditioning, by acting on the forebrain GABAA-Rs that harbor the α1 subunit. To test this, we used global knockout mice that completely lack the α1 subunit and forebrain-specific, conditional knockout mice that lack the α1 subunit only in the hippocampus, cortex, and amygdala. Both knockout mice were 75 to 145% less sensitive to the amnestic effects of the inhaled anesthetic isoflurane. These results indicate that α1-containing GABAA-Rs in the hippocampus, amygdala, and/or cortex influence the amnestic effects of inhaled anesthetics and may be an important molecular target of the drug isoflurane.

Original languageEnglish (US)
Pages (from-to)61-68
Number of pages8
JournalMolecular pharmacology
Volume68
Issue number1
DOIs
StatePublished - Jul 2005

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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    Sonner, J. M., Cascio, M., Xing, Y., Fanselow, M. S., Kralic, J. E., Leslie Morrow, A., Korpi, E. R., Hardy, S., Sloat, B., Eger, E. I., & Homanics, G. E. (2005). α1 subunit-containing GABA type a receptors in forebrain contribute to the effect of inhaled anesthetics on conditioned fear. Molecular pharmacology, 68(1), 61-68. https://doi.org/10.1124/mol.104.009936