A critical review of ethanol effects on neuronal firing: A metabolic perspective

• Published in: Alcohol, clinical & experimental research clinical & experimental research, 2024-03, Vol.48 (3), p.450-458
• Main Authors: Popova, Dina, Sun, Jacquelyne, Chow, Hei‐Man, Hart, Ronald P.
• Format: Article
• Language: English
• Subjects: alcohol metabolism; excitability; neuron
• ISSN: 2993-7175; 2993-7175
• DOI: 10.1111/acer.15266

Ethanol metabolism is relatively understudied in neurons, even though changes in neuronal metabolism are known to affect their activity. Recent work demonstrates that ethanol is preferentially metabolized over glucose as a source of carbon and energy, and it reprograms neurons to a state of reduced energy potential and diminished capacity to utilize glucose once ethanol is exhausted. Ethanol intake has been associated with changes in neuronal firing and specific brain activity (EEG) patterns have been linked with risk for alcohol use disorder (AUD). Furthermore, a haplotype of the inwardly rectifying potassium channel subunit, GIRK2, which plays a critical role in regulating excitability of neurons, has been linked with AUD and shown to be directly regulated by ethanol. At the same time, overexpression of GIRK2 prevents ethanol‐induced metabolic changes. Based on the available evidence, we conclude that the mechanisms underlying the effects of ethanol on neuronal metabolism are a novel target for developing therapies for AUD. This review proposes that neuronal metabolic mechanisms underlying effects of ethanol represent a novel therapeutic strategy for alcohol use disorder (AUD). Neuronal ethanol metabolism induces a state of reduced energy potential and diminished capacity to utilize glucose, which could modulate neuronal firing and specific brain activity (EEG) patterns to increase the risk of AUD. A variant of GIRK2, an inwardly rectifying potassium channel subunit that affects excitability and is linked with AUD, was also shown to be regulated by ethanol.