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Role of GABAA receptors in alcohol use disorders suggested by chronic intermittent ethanol (CIE) rodent model

Overview of attention for article published in Molecular Brain, September 2017
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • High Attention Score compared to outputs of the same age and source (99th percentile)

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Title
Role of GABAA receptors in alcohol use disorders suggested by chronic intermittent ethanol (CIE) rodent model
Published in
Molecular Brain, September 2017
DOI 10.1186/s13041-017-0325-8
Pubmed ID
Authors

Richard W. Olsen, Jing Liang

Abstract

GABAergic inhibitory transmission is involved in the acute and chronic effects of ethanol on the brain and behavior. One-dose ethanol exposure induces transient plastic changes in GABAA receptor subunit levels, composition, and regional and subcellular localization. Rapid down-regulation of early responder δ subunit-containing GABAA receptor subtypes mediating ethanol-sensitive tonic inhibitory currents in critical neuronal circuits corresponds to rapid tolerance to ethanol's behavioral responses. Slightly slower, α1 subunit-containing GABAA receptor subtypes mediating ethanol-insensitive synaptic inhibition are down-regulated, corresponding to tolerance to additional ethanol behaviors plus cross-tolerance to other GABAergic drugs including benzodiazepines, anesthetics, and neurosteroids, especially sedative-hypnotic effects. Compensatory up-regulation of synaptically localized α4 and α2 subunit-containing GABAA receptor subtypes, mediating ethanol-sensitive synaptic inhibitory currents follow, but exhibit altered physio-pharmacology, seizure susceptibility, hyperexcitability, anxiety, and tolerance to GABAergic positive allosteric modulators, corresponding to heightened alcohol withdrawal syndrome. All these changes (behavioral, physiological, and biochemical) induced by ethanol administration are transient and return to normal in a few days. After chronic intermittent ethanol (CIE) treatment the same changes are observed but they become persistent after 30 or more doses, lasting for at least 120 days in the rat, and probably for life. We conclude that the ethanol-induced changes in GABAA receptors represent aberrant plasticity contributing critically to ethanol dependence and increased voluntary consumption. We suggest that the craving, drug-seeking, and increased consumption in the rat model are tied to ethanol-induced plastic changes in GABAA receptors, importantly the development of ethanol-sensitive synaptic GABAA receptor-mediating inhibitory currents that participate in maintained positive reward actions of ethanol on critical neuronal circuits. These probably disinhibit nerve endings of inhibitory GABAergic neurons on dopamine reward circuit cells, and limbic system circuits mediating anxiolysis in hippocampus and amygdala. We further suggest that the GABAA receptors contributing to alcohol dependence in the rat and presumably in human alcohol use disorders (AUD) are the ethanol-induced up-regulated subtypes containing α4 and most importantly α2 subunits. These mediate critical aspects of the positive reinforcement of ethanol in the dependent chronic user while alleviating heightened withdrawal symptoms experienced whenever ethanol is absent. The speculative conclusions based on firm observations are readily testable.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 107 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 107 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 27 25%
Student > Bachelor 14 13%
Student > Master 10 9%
Researcher 8 7%
Student > Doctoral Student 5 5%
Other 13 12%
Unknown 30 28%
Readers by discipline Count As %
Neuroscience 23 21%
Pharmacology, Toxicology and Pharmaceutical Science 10 9%
Medicine and Dentistry 9 8%
Biochemistry, Genetics and Molecular Biology 6 6%
Psychology 6 6%
Other 15 14%
Unknown 38 36%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 11. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 01 June 2021.
All research outputs
#2,999,877
of 23,926,844 outputs
Outputs from Molecular Brain
#142
of 1,154 outputs
Outputs of similar age
#55,782
of 320,899 outputs
Outputs of similar age from Molecular Brain
#1
of 15 outputs
Altmetric has tracked 23,926,844 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,154 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.0. This one has done well, scoring higher than 86% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 320,899 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 99% of its contemporaries.