Activation of extrasynaptic δ-GABAA receptors globally or within the posterior-VTA has estrous-dependent effects on consumption of alcohol and estrous-independent effects on locomotion
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Recent reports support higher than expected rates of binge alcohol consumption among women and girls. Unfortunately, few studies have assessed the mechanisms underlying this pattern of intake in females. Studies in males suggest that alcohol concentrations relevant to the beginning stages of binge intoxication may selectively target tonic GABAergic inhibition mediated by GABA A receptor subtypes expressing the δ-subunit protein (δ-GABA A Rs). Indeed, administration of agonists that interact with these δ-GABA A Rs prior to alcohol access can abolish binge drinking behavior in male mice. These δ-GABA A Rs have also been shown to exhibit estrous-dependent plasticity in regions relevant to drug taking behavior, like the hippocampus and periaqueductal gray. The present experiments were designed to determine whether the estrous cycle would alter binge drinking, or our ability to modulate this pattern of alcohol use with THIP, an agonist with high selectivity and efficacy at δ-GABA A Rs. Using the Drinking-in-the-Dark (DID) binge-drinking model, regularly cycling female mice were given 2h of daily access to alcohol (20%v/v). Vaginal cytology or vaginal impedance was assessed after drinking sessions to track estrous status. There was no fluctuation in binge drinking associated with the estrous cycle. Both Intra-posterior-VTA administration of THIP and systemic administration of the drug was also associated with an estrous cycle dependent reduction in drinking behavior. Pre-treatment with finasteride to inhibit synthesis of 5α-reduced neurosteroids did not disrupt THIP's effects. Analysis of δ-subunit mRNA from posterior-VTA enriched tissue samples revealed that expression of this GABA A receptor subunit is elevated during diestrus in this region. Taken together, these studies demonstrate that δGABA A Rs in the VTA are an important target for binge drinking in females and confirm that the estrous cycle is an important moderator of the pharmacology of this GABA A receptor subtype.
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δGABAARs in the VTA have been implicated in the consumption of ethanol, although only under specific circumstances.
“δGABAARs in the VTA have also been implicated in the consumption of ethanol, although only under specific circumstances [114].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [114]
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An emerging circuit pharmacology of GABAA receptors
Engin, E., Benham, R. S., & Rudolph, U. (2018) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2018.04.003 · Cited by 225 · see citing works
- Authors
- Melón, L. C., Nolan, Z. T., Colar, D., Moore, E. M., & Boehm, S. L.
- Affiliations
- Tufts University (US)
- Pennsylvania State University (US)
- Indiana University Indianapolis (US)
- San Diego State University (US)
- Corresponding author
- Boehm, Stephen L.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 95
- Pages
- 65-75
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC5623082
- OpenAlex
- W2756440222
- Cited by
- 18
- References
- 91
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 4 · 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- PMC
- Funders
- National Institutes of Health (AA016789, F31AA018910, T32 AA07462, K12GM074869)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- estrous cycle, binge drinking, alcohol consumption, finasteride, diestrus, locomotion
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Female, Hippocampus, Isoxazoles, Locomotion, Male, Mice, Inbred C57BL, Periaqueductal Gray, Receptors, GABA-A, Synapses, Ventral Tegmental Area, Estrous Cycle, Mice, GABA-A Receptor Agonists, Binge Drinking
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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