Cited by 59Neuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on BehaviorNeuropeptides and Animal Physiology

Chronic intermittent ethanol exposure dysregulates a GABAergic microcircuit in the bed nucleus of the stria terminalis

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Pati, Dipanwita, Marcinkiewcz, Catherine A., DiBerto, Jeffrey F., Cogan, Elizabeth S., McElligott, Zoe A., Kash, Thomas L.·2020·Neuropharmacology

Abstract

Neuroadaptations in brain regions that regulate emotional and reward-seeking behaviors have been suggested to contribute to pathological behaviors associated with alcohol-use disorder. One such region is the bed nucleus of the stria terminalis (BNST), which has been linked to both alcohol consumption and alcohol withdrawal-induced anxiety and depression. Recently, we identified a GABAergic microcircuit in the BNST that regulates anxiety-like behavior. In the present study, we examined how chronic alcohol exposure alters this BNST GABAergic microcircuit in mice. We selectively targeted neurons expressing corticotropin releasing factor (CRF) using a CRF-reporter mouse line and combined retrograde labeling to identify BNST projections to the ventral tegmental area (VTA) and lateral hypothalamus (LH). Following 72 h of withdrawal from four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure, the excitability of a sub-population of putative local CRF neurons that did not project to either VTA or LH (CRF non-VTA/LH neurons) was increased. Withdrawal from CIE also increased excitability of non-CRF BNST neurons that project to both LH and VTA (BNST non-CRF-proj neurons). Furthermore, both populations of neurons had a reduction in spontaneous EPSC amplitude while frequency was unaltered. Withdrawal from chronic alcohol was accompanied by a significant increase in spontaneous IPSC frequency selectively in the BNST non-CRF-proj neurons. Together, these data suggest that withdrawal from chronic ethanol dysregulates local CRF-GABAergic microcircuit to inhibit anxiolytic outputs of the BNST which may contribute to enhanced anxiety during alcohol withdrawal and drive alcohol-seeking behavior. This article is part of the special issue on 'Neuropeptides'.

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  1. Pleil KE, Lowery-Gionta EG, Crowley NA, Li C, Marcinkiewcz CA, Rose JH, (2015b). Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala. Neuropharmacology 99: 735– 749. 26188147 PMC4781662
  2. Silberman Y, Matthews RT, Winder DG (2013b). A Corticotropin Releasing Factor Pathway for Ethanol Regulation of the Ventral Tegmental Area in the Bed Nucleus of the Stria Terminalis. J Neurosci 33: 950 LP – 960. 23325234 PMC3566560

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Authors
Pati, D., Marcinkiewcz, C. A., DiBerto, J. F., Cogan, E. S., McElligott, Z. A., & Kash, T. L.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Kash, Thomas L.
Venue
Neuropharmacology
Publisher
Elsevier BV
Published
2020-05
Volume
168
Pages
107759
ISSN
0028-3908 (ISSN-L)
OpenAlex
W2971817407
Cited by
59
References
62
Citations by year
2026: 4 · 2025: 7 · 2024: 9 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 10 · 2019: 1
FWCI
3.70
Type
journal article
Language
en
Open access
Locations
  • Neuropharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
  • UNC Libraries
Funders
National Institute on Alcohol Abuse and Alcoholism (U01 AA020911, P60 AA011605, U24 AA025475, K01AA023555, K99A024215, R01 AA019454)
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords
chronic intermittent ethanol, alcohol withdrawal, bed nucleus of the stria terminalis, corticotropin-releasing factor, CRF neurons, neuronal excitability, spontaneous inhibitory postsynaptic currents, spontaneous excitatory postsynaptic currents, ventral tegmental area, lateral hypothalamus, anxiety, alcoholism, alcohol seeking
MeSH terms
Ethanol, Animals, Male, Mice, Inbred C57BL, Mice, Transgenic, Nerve Net, Organ Culture Techniques, Septal Nuclei, Mice, GABAergic Neurons

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