TY - JOUR T1 - α1 Subunit-Containing GABA Type A Receptors in Forebrain Contribute to the Effect of Inhaled Anesthetics on Conditioned Fear JF - Molecular Pharmacology JO - Mol Pharmacol SP - 61 LP - 68 DO - 10.1124/mol.104.009936 VL - 68 IS - 1 AU - James M. Sonner AU - Mike Cascio AU - Yilei Xing AU - Michael S. Fanselow AU - Jason E. Kralic AU - A. Leslie Morrow AU - Esa R. Korpi AU - Steven Hardy AU - Brian Sloat AU - Edmond I. Eger II AU - Gregg E. Homanics Y1 - 2005/07/01 UR - http://molpharm.aspetjournals.org/content/68/1/61.abstract N2 - 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. ER -