期刊
JOURNAL OF NEUROSCIENCE
卷 30, 期 21, 页码 7139-7151出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0693-10.2010
关键词
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资金
- National Institutes of Health (NIH) [DA019624, F32 MH073389-01]
- Center for Behavioral Neuroscience (National Science Foundation) [IBN-987675]
- Burroughs Wellcome Fund
- NIH/National Center for Research Resources [P51RR000165]
The heterogeneity and distribution of GABA(A) receptor subunits mediates differential roles in behavior. It is thought that particular behavioral responses to benzodiazepine (BZ) ligands might be associated with an action at a regionally defined receptor subtype. However, the role of specific GABA(A) receptor subtypes in particular brain regions is less clear. Such detailed knowledge of regional alpha 1-GABA(A) receptor function will advance our understanding of the neural circuitry underlying the role of GABA(A) receptors and the effects of GABA(A)-modulating drugs on behavior. By combining inducible, site-specific alpha 1 subunit deletion, using a lentivirus expressing Cre-recombinase in mice with the alpha 1 subunit gene flanked by loxP sites, we examine baseline and pharmacological effects of deletion of amygdala alpha 1-GABA(A) receptors. We find that amygdala-specific reduction of alpha 1 receptor subunits does not affect mRNA or protein levels of amygdala alpha 2 or alpha 3 subunit receptors. Nor does this inducible reduction affect baseline locomotion or measures of anxiety. However, we also find that this inducible, site-specific deletion does disrupt the normal sedative-locomotor inhibition as well as the anticonvulsive effects, of two distinct BZ-site ligands, diazepam and zolpidem, which is relatively alpha 1-subunit selective. These data, using inducible, region and subunit-specific deletion, combined with pharmacogenetic approaches, demonstrate that amygdala expression of the alpha 1-GABA(A) receptor subunit is required for normal BZ effects on sedation, locomotion, and seizure inhibition, but not for anxiolysis.
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