TY - JOUR
T1 - α1 subunit-containing GABA type a receptors in forebrain contribute to the effect of inhaled anesthetics on conditioned fear
AU - Sonner, James M.
AU - Cascio, Mike
AU - Xing, Yilei
AU - Fanselow, Michael S.
AU - Kralic, Jason E.
AU - Leslie Morrow, A.
AU - Korpi, Esa R.
AU - Hardy, Steven
AU - Sloat, Brian
AU - Eger, Edmond I.
AU - Homanics, Gregg E.
PY - 2005/7
Y1 - 2005/7
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.
AB - 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.
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U2 - 10.1124/mol.104.009936
DO - 10.1124/mol.104.009936
M3 - Article
C2 - 15833735
AN - SCOPUS:22344454013
SN - 0026-895X
VL - 68
SP - 61
EP - 68
JO - Molecular pharmacology
JF - Molecular pharmacology
IS - 1
ER -