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Cited by 168Neuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors StudyReceptor Mechanisms and Signaling

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

GABAA receptor alpha-1 subunit deletion alters receptor subtype assembly, pharmacological and behavioral responses to benzodiazepines and zolpidem

Kralic, J.E., O’Buckley, T.K., Khisti, R.T., Hodge, C.W., Homanics, G.E., Morrow, A.L.·2002·Neuropharmacology
DOI 10.1016/s0028-3908(02)00174-0
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Abstract

Potentiation of GABA(A) receptor activation through allosteric benzodiazepine (BZ) sites produces the anxiolytic, anticonvulsant and sedative/hypnotic effects of BZs. Using a mouse line lacking alpha1 subunit expression, we investigated the contribution of the alpha1 subunit to GABA(A) receptor pharmacology, function and related behaviors in response to BZ site agonists. Competitive [(3)H]flunitrazepam binding experiments using the Type I BZ site agonist, zolpidem, and the Type I and II BZ site non-specific agonist, diazepam, demonstrated the complete loss of Type I BZ binding sites in alpha1(-/-) mice and a compensatory increase in Type II BZ binding sites (41+/-6%, P<0.002). Chloride uptake analysis in alpha1(-/-) mice revealed an increase (108+/-10%, P<0.001) in the efficacy (E(max)) of flunitrazepam while the EC(50) of zolpidem was increased 495+/-26% (alpha1(+/+): 184+/-56 nM; alpha1(-/-): 1096+/-279 nM, P<0.01). An anxiolytic effect of diazepam was detected in both alpha1(+/+) and alpha1(-/-) mice as measured on the elevated plus maze; however, alpha1(-/-) mice exhibited a greater percentage of open arm entries and percentage of open arm time following 0.6 mg/kg diazepam. Furthermore, alpha1(-/-) mice were more sensitive to the motor impairing/sedative effects of diazepam (1-10 mg/kg) as measured by locomotor activity in the open field. Knockout mice were insensitive to the anticonvulsant effect of diazepam (1-15 mg/kg, P<0.001). The hypnotic effect of zolpidem (60 mg/k…

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  • Zolpidem is a high-affinity positive modulator of GABAA receptors that enhances GABAergic transmission by binding to the alpha1 subunit.

    “Zolpidem (Ambien) is a high-affinity positive modulator of GABAA receptors, that enhances GABAergic transmission by binding to the alpha1 subunit91.”

    From Norepinephrine-mediated slow vasomotion drives glymphatic clearance during sleep (2025) · cites this paper as [91]

Citations

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Metadata

Authors
Kralic, J. E., O’Buckley, T. K., Khisti, R. T., Hodge, C. W., Homanics, G. E., & Morrow, A. L.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • University of Pittsburgh (US)
Corresponding author
Morrow, A.L.
ORCID
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2002-09
Volume
43
Issue
4
Pages
685-694
ISSN
0028-3908 (ISSN-L)
DOI
10.1016/s0028-3908(02)00174-0
OpenAlex
W1993462849
Cited by
168
References
1
Citations by year
2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 2 · 2019: 7 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 3 · 2014: 10 · 2013: 2 · 2012: 9
FWCI
4.30
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
benzodiazepine binding site, zolpidem, diazepam, flunitrazepam, chloride uptake, anxiolytic effects, sedative-hypnotic effects, anticonvulsant activity, knockout mice
MeSH terms
Zolpidem, Animals, Anticonvulsants, Behavior, Animal, Benzodiazepines, Chlorides, Diazepam, Postural Balance, Exploratory Behavior, Female, Flunitrazepam, Hypnotics and Sedatives, Male, Motor Activity, Muscimol, Pyridines, Radioligand Assay, Receptors, GABA-A, Seizures, Anti-Anxiety Agents, Gene Deletion, Mice, Knockout, GABA Agonists, GABA Modulators, Mice

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