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Cited by 64Stress Responses and CortisolAlcohol Consumption and Health EffectsNeurotransmitter Receptor Influence on Behavior

Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors

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Somkuwar, Sucharita S., Vendruscolo, Leandro F., Fannon, McKenzie J., Schmeichel, Brooke E., Nguyen, Tran Bao, Guevara, Jasmin, Sidhu, Harpreet, Contet, Candice +2 more·2017·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2017.06.006PMC PMC5557646
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Abstract

Alcohol dependence is linked to dysregulation of the hypothalamic-pituitary-adrenal axis. Here, we investigated effects of repeated ethanol intoxication-withdrawal cycles (using chronic intermittent ethanol vapor inhalation; CIE) and abstinence from CIE on peak and nadir plasma corticosterone (CORT) levels. Irritability- and anxiety-like behaviors as well as glucocorticoid receptors (GR) in the medial prefrontal cortex (mPFC) were assessed at various intervals (2h-28d) after cessation of CIE. Results show that peak CORT increased during CIE, transiently decreased during early abstinence (1-11d), and returned to pre-abstinence levels during protracted abstinence (17-27d). Acute withdrawal from CIE enhanced aggression- and anxiety-like behaviors. Early abstinence from CIE reduced anxiety-like behavior. mPFC-GR signaling (indexed by relative phosphorylation of GR at Ser211) was transiently decreased when measured at time points during early and protracted abstinence. Further, voluntary ethanol drinking in CIE (CIE-ED) and CIE-naïve (ED) rats, and effects of CIE-ED and ED on peak CORT levels and mPFC-GR were investigated during acute withdrawal (8h) and protracted abstinence (28d). CIE-ED and ED increased peak CORT during drinking. CIE-ED and ED decreased expression and signaling of mPFC-GR during acute withdrawal, an effect that was reversed by systemic mifepristone treatment. CIE-ED and ED demonstrate robust reinstatement of ethanol seeking during protracted abstinence and show increases in mPFC-GR expression. Collectively, the data demonstrate that acute withdrawal from CIE produces robust alterations in GR signaling, CORT and negative affect symptoms which could facilitate excessive drinking. The findings also show that CIE-ED and ED demonstrate enhanced relapse vulnerability triggered by ethanol cues and these changes are partially mediated by altered GR expression in the mPFC. Taken together, transition to alcohol dependence could be accompanied by alterations in mPFC stress-related pathways that may increase negative emotional symptoms and increase vulnerability to relapse.

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  • Heightened irritability-related reactivity during alcohol withdrawal can persist for at least two weeks into abstinence.

    “Preclinical studies using this paradigm reveal increased irritability-related responses during alcohol withdrawal, with evidence suggesting that such heightened reactivity can persist for at least two weeks into abstinence (Somkuwar et al. 2017; Kimbrough et al. 2020).”

    From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Somkuwar et al. 2017

  • Preclinical studies using the irritability-like paradigm reveal increased irritability-related responses during alcohol withdrawal.

    “Preclinical studies using this paradigm reveal increased irritability-related responses during alcohol withdrawal, with evidence suggesting that such heightened reactivity can persist for at least two weeks into abstinence (Somkuwar et al. 2017; Kimbrough et al. 2020).”

    From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Somkuwar et al. 2017

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Authors
Somkuwar, S. S., Vendruscolo, L. F., Fannon, M. J., Schmeichel, B. E., Nguyen, T. B., Guevara, J., Sidhu, H., Contet, C., Zorrilla, E. P., & Mandyam, C. D.
Affiliations
  • VA San Diego Healthcare System (US)
  • National Institute on Drug Abuse (US)
  • University of California San Diego (US)
  • Scripps Research Institute (US)
Corresponding author
Somkuwar, Sucharita S.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2017-10
Volume
84
Pages
17-31
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2017.06.006
PMC
PMC5557646
OpenAlex
W2624994890
Cited by
64
References
119
Citations by year
2026: 1 · 2025: 5 · 2024: 3 · 2023: 5 · 2022: 11 · 2021: 4 · 2020: 15 · 2019: 7 · 2018: 12 · 2017: 1
FWCI
5.21
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Alcoholism and Alcohol Abuse (NIAAA) and National Institute on Drug Abuse (AA020098, AA06420, DA034140)
  • Veterans Medical Research Foundation start-up funds
  • Skaggs School of Pharmacy and Pharmaceutical Sciences
  • NIDA
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
ethanol withdrawal, alcoholism, corticosterone, glucocorticoid receptor signaling, hypothalamic-pituitary-adrenal axis, medial prefrontal cortex, anxiety-like behavior, aggression, relapse vulnerability, mifepristone, negative affect
MeSH terms
Alcohol Drinking, Ethanol, Alcoholism, Animals, Corticosterone, Disease Models, Animal, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Receptors, Glucocorticoid, Stress, Psychological, Substance Withdrawal Syndrome, Signal Transduction, Rats, Wistar, Prefrontal Cortex, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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