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Molecular Pharmacology

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Research ArticleArticle

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 II and Gregg E. Homanics
Molecular Pharmacology July 2005, 68 (1) 61-68; DOI: https://doi.org/10.1124/mol.104.009936
James M. Sonner
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Mike Cascio
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Yilei Xing
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Michael S. Fanselow
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Jason E. Kralic
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A. Leslie Morrow
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Esa R. Korpi
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Steven Hardy
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Brian Sloat
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Edmond I. Eger II
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Gregg E. Homanics
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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.

  • Received December 8, 2004.
  • Accepted April 15, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 68 (1)
Molecular Pharmacology
Vol. 68, Issue 1
1 Jul 2005
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Research ArticleArticle

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 and Gregg E. Homanics
Molecular Pharmacology July 1, 2005, 68 (1) 61-68; DOI: https://doi.org/10.1124/mol.104.009936

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Research ArticleArticle

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 and Gregg E. Homanics
Molecular Pharmacology July 1, 2005, 68 (1) 61-68; DOI: https://doi.org/10.1124/mol.104.009936
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