Evidence map›Paper›PMID 34995754›Full record

ArticleNeurobiology of disease2022

Alcohol dependence and withdrawal increase sensitivity of central amygdalar GABAergic synapses to the glucocorticoid receptor antagonist mifepristone in male rats.

Sophia Khom, Larry Rodriguez, Pauravi Gandhi, Dean Kirson, Michal Bajo, Christopher S Oleata, Leandro F Vendruscolo, Barbara J Mason, Marisa Roberto

Open access · goldAbstract read
In one paragraph

Article in Neurobiology of disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
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  10. FKBP5 inhibitors modulate alcohol drinking and trauma-related behaviors in a model of comorbid post-traumatic stress and alcohol use disorder.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Sophia KhomDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America; Department of Pharmaceutical Sciences, University of Vienna, Althanstrasse 14, A-1090 Vienna, Austria.
Larry RodriguezDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America.
Pauravi GandhiDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America.
Dean KirsonDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America; Department of Pharmacology, Addiction Science, and Toxicology, University of Tennessee Health Science Center, 71 S Manassas, Memphis, TN 38163, United States of America.
Michal BajoDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America.
Christopher S OleataDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America.
Leandro F VendruscoloIntegrative Neuroscience Research Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, 251 Bayview Blvd., Baltimore, MD 21224, United States of America.
Barbara J MasonDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America.
Marisa RobertoDepartment of Molecular Medicine, Scripps Research, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States of America. Electronic address: mroberto@scripps.edu.
Torrey Pines Institute For Molecular Studies · USScripps Institution of Oceanography · USScripps (United States) · USNational Institute on Drug Abuse · USUniversity of Tennessee Health Science Center · US

Funding

Viral Vector CoreP60AA006420 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI AMANDA J ROBERTS · 2003 to 2026
$46.3M
Neurpsychopharmacology-Multidisciplinary TrainingT32AA007456 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI MARISA ROBERTO · 1985 to 2026
$13.4M
Electrophysiology of alcohol in extended amygdelaU01AA013498 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI MARISA ROBERTO · 2001 to 2026
$12.6M
SYSTEMIC NEUROPHARMACOLOGYP50AA006420 · NIAAA · SCRIPPS RESEARCH INSTITUTE · PI SIGGINS, GEORGE ROBERT · 1985 to 2002
$5.1M
Integrative Neuroscience Initiative on AlcoholismU24AA025479 · NIAAA · UNIVERSITY OF TEXAS AT AUSTIN · PI ROBERT O. MESSING · 2017 to 2026
$5.0M
Neuroplasticity of the Extended Amygdala CRF circuitry in alcohol dependenceR01AA021491 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2013 to 2024
$3.9M
Gene-environment interaction: the brain CRF system in alcohol preferring msP ratsR37AA017447 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2016 to 2025
$3.7M
Glucocorticoid Antagonist Treatment of Alcohol Use DisorderR01AA023152 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI MASON, BARBARA J · 2014 to 2018
$2.9M
Neuroimmune mechanisms in stress and alcohol comorbidityR01AA027700 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2019 to 2023
$2.4M
Gene-environment interaction: the brain CRF system in alcohol preferring msP ratsR01AA017447 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI ROBERTO, MARISA · 2009 to 2013
$1.8M
Hypothalamic oxytocin influence on extended amygdala CRF neurons in alcohol dependenceR00AA026638 · NIAAA · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI KIRSON, DEAN · 2021 to 2023
$842k
Hypothalamic oxytocin influence on extended amygdala CRF neurons in alcohol dependenceK99AA026638 · NIAAA · SCRIPPS RESEARCH INSTITUTE, THE · PI KIRSON, DEAN · 2018 to 2020
$419k
NIAAA NIH HHS K99 AA026638NIAAA NIH HHS P50 AA006420NIAAA NIH HHS P60 AA006420NIAAA NIH HHS R00 AA026638NIAAA NIH HHS R01 AA017447NIAAA NIH HHS R01 AA021491NIAAA NIH HHS R01 AA023152NIAAA NIH HHS R01 AA027700NIAAA NIH HHS R37 AA017447NIAAA NIH HHS T32 AA007456NIAAA NIH HHS U01 AA013498NIAAA NIH HHS U24 AA025479
6 · The paper itself

Abstract

Aberrant glucocorticoid signaling via glucocorticoid receptors (GR) plays a critical role in alcohol use disorder (AUD). Acute alcohol withdrawal and protracted abstinence in dependent rats are associated with increased GR signaling and changes in GR-mediated transcriptional activity in the rat central nucleus of the amygdala (CeA). The GR antagonist mifepristone decreases alcohol consumption in dependent rats during acute withdrawal and protracted abstinence. Regulation of CeA synaptic activity by GR is currently unknown. Here, we utilized mifepristone and the selective GR antagonist CORT118335 (both at 10 μM) as pharmacological tools to dissect the role of GR on GABA transmission in male, adult Sprague-Dawley rats using slice electrophysiology. We subjected rats to chronic intermittent alcohol vapor exposure for 5-7 weeks to induce alcohol dependence. A subset of dependent rats subsequently underwent protracted alcohol withdrawal for 2 weeks, and air-exposed rats served as controls. Mifepristone reduced the frequency of pharmacologically-isolated spontaneous inhibitory postsynaptic currents (sIPSC) in the CeA (medial subdivision) without affecting postsynaptic measures in all groups, suggesting decreased GABA release with the largest effect in dependent rats. CORT118335 did not significantly alter GABA transmission in naïve, but decreased sIPSC frequency in dependent rats. Similarly, mifepristone decreased amplitudes of evoked inhibitory postsynaptic potentials only in dependent rats and during protracted withdrawal. Collectively, our study provides insight into regulation of CeA GABAergic synapses by GR. Chronic ethanol enhances the efficiency of mifepristone and CORT118335, thus highlighting the potential of drugs targeting GR as a promising pharmacological avenue for the treatment of AUD.

Indexed as

AlcoholismAmygdalaAnimalsGABAergic NeuronsHormone AntagonistsInhibitory Postsynaptic PotentialsMaleMifepristoneRatsRats, Sprague-DawleyReceptors, GlucocorticoidSynapsesHormone AntagonistsMifepristoneReceptors, GlucocorticoidAlcohol use disorderCentral amygdalaeIPSPElectrophysiologyGABAGlucocorticoid receptorsMifepristonesIPSCSynaptic transmission

Identifiers

PMID34995754
PMCPMC9301881
OpenAlexW4206355166

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.