Cited by 42Neuroscience and Neuropharmacology ResearchEpilepsy research and treatmentNicotinic Acetylcholine Receptors Study

Amygdala-Specific Reduction of α1-GABA A Receptors Disrupts the Anticonvulsant, Locomotor, and Sedative, But Not Anxiolytic, Effects of Benzodiazepines in Mice

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Heldt, Scott A., Ressler, Kerry J.·2010·The Journal of Neuroscience

Abstract

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 alpha1-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 alpha1 subunit deletion, using a lentivirus expressing Cre-recombinase in mice with the alpha1 subunit gene flanked by loxP sites, we examine baseline and pharmacological effects of deletion of amygdala alpha1-GABA(A) receptors. We find that amygdala-specific reduction of alpha1 receptor subunits does not affect mRNA or protein levels of amygdala alpha2 or alpha3 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 alpha1-subunit selective. These data, using inducible, region and subunit-specific deletion, combined with pharmacogenetic approaches, demonstrate that amygdala expression of the alpha1-GABA(A) receptor subunit is required for normal BZ effects on sedation, locomotion, and seizure inhibition, but not for anxiolysis.

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Crossref · 10.1523/jneurosci.0693-10.2010

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  • α1GABAARs of the BLA do not seem important for anxiety-related behaviors in the elevated plus maze.

    “While playing such a substantial role in the acquisition and expression of conditioned fear, α1GABAARs of the BLA do not seem to be important for anxiety-related behaviors in the elevated plus maze (see Box 5) [25]”

    From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [25]

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Research works printed but not linked: 2

  1. Rudolph U Crestani F Benke D Brunig I Benson JA Fritschy J-M Martin JR Bluethmann H Mohler H 1999b Benzodiazepine actions mediated by specific [gamma]-aminobutyric acidA receptor subtypes Nature 401 796 800 10548105
  2. Sanger DJ Morel E Perrault G 1996b Comparison of the pharmacological profiles of the hypnotic drugs, zaleplon and zolpidem European Journal of Pharmacology 313 35 42 8905326

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Authors
Heldt, S. A., & Ressler, K. J.
Affiliations
  • Emory University (US)
  • Howard Hughes Medical Institute (US)
Venue
The Journal of Neuroscience
Published
2010-05-26
Volume
30
Issue
21
Pages
7139-7151
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2095315913
Cited by
42
References
84
Citations by year
2026: 3 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 3 · 2021: 1 · 2018: 5 · 2017: 5 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 3
FWCI
1.29
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Science Foundation
  • Howard Hughes Medical Institute
  • Burroughs Wellcome Fund (DA019624, P51RR000165)
  • National Institutes of Health
  • Yerkes National Primate Research Center, Emory University (P51RR000165)
  • National Institute of Mental Health (RC1MH088467, F32MH073389)
  • National Institute on Drug Abuse (R01DA019624, DA-019624)
  • National Center for Research Resources (P51RR000165)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords
amygdala, benzodiazepines, diazepam, zolpidem, anticonvulsant activity, sedation, locomotor inhibition, anxiolysis, GABAA receptor subunits, Cre-loxP system, pharmacogenetics
MeSH terms
Zolpidem, Amygdala, Animals, Animals, Newborn, Anticonvulsants, Benzodiazepines, Cell Line, Transformed, Cells, Cultured, Disease Models, Animal, Dose-Response Relationship, Drug, Epilepsy, Exploratory Behavior, Gene Expression Regulation, Hippocampus, Humans, Hypnotics and Sedatives, Locomotion, Male, Mice, Inbred C57BL, Mice, Transgenic, Pentylenetetrazole, Pyridines, Receptors, GABA-A, RNA, Messenger, Anti-Anxiety Agents, Transfection, Maze Learning, Green Fluorescent Proteins, Mice

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