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The neurobiological markers of acute alcohol’s subjective effects in humans

Abstract

The ingestion of alcohol yields acute biphasic subjective effects: stimulation before sedation. Despite their predictive relevance to the development of alcohol use disorders (AUD), the neurobiological markers accounting for the biphasic effects of alcohol remain poorly understood in humans. Informed by converging lines of evidence, this study tested the hypothesis that alcohol ingestion acutely increases gamma-aminobutyric acid (GABA)-mediated inhibition, which would positively and negatively predict the feeling of stimulation and sedation, respectively. To do so, healthy participants (n = 20) ingested a single dose of 94% ABV alcohol (males: 1.0 ml/kg; females: 0.85 ml/kg) in a randomized placebo-controlled cross-over design. The alcohol’s biphasic effects were assessed with the Brief-Biphasic Alcohol Effects Scale, and non-invasive neurobiological markers were measured with transcranial magnetic stimulation, before and every 30 min (up to 120 min) after the complete ingestion of the beverage. Results showed that acute alcohol ingestion selectively increased the duration of the cortical silent period (CSP) as compared to placebo, suggesting that alcohol increases non-specific GABAergic inhibition. Importantly, CSP duration positively and negatively predicted increases in the feeling of stimulation and sedation, respectively, suggesting that stimulation emerges as GABAergic inhibition increases and that sedation emerges as GABAergic inhibition returns to baseline values. Overall, these results suggest that modulations of GABAergic inhibition are central to the acute biphasic subjective effects of alcohol, providing a potential preventive target to curb the progression of at-risk individuals to AUD.

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Fig. 1: Overview of the within-subject and placebo-controlled paradigm.
Fig. 2: BrAC and B-BAES results.
Fig. 3: TMS results.

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Funding

This work was supported by grants from the Fonds de la Recherche du Québec- Santé [FRQS, Grant 33140] and the Natural Sciences and Engineering Research Council of Canada [NSERC; Grant RGPIN-2017-05510] awarded to JFL.

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RH designed the experiment, conducted the analyses, prepared the figures, and wrote the manuscript. OD collected the data, conducted the analyses, prepared the figures, and helped to write the manuscript. CB and MLR collected the data. HT and PMB revised the manuscript. JFL helped to design the experiment and revised the manuscript.

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Correspondence to Jean-Francois Lepage.

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Hamel, R., Demers, O., Boileau, C. et al. The neurobiological markers of acute alcohol’s subjective effects in humans. Neuropsychopharmacol. (2022). https://doi.org/10.1038/s41386-022-01354-w

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