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bioRxiv · 10.1101/283358

Acute alcohol administration dampens threat-related activation in the central extended amygdala

Hur, J.·Kaplan, C. M.·Smith, J. F.·Bradford, D. E.·Fox, A. S.·Curtin, J. J.·Shackman, A. J.
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Abstract

Alcohol abuse is common, imposes a staggering burden on public health, and is challenging to treat, underscoring the need to develop a deeper understanding of the underlying neurobiology. When administered acutely, ethyl alcohol reduces threat reactivity in humans and other animals, and there is growing evidence that threat-dampening and related negative reinforcement mechanisms support the etiology and recurrence of alcohol and other kinds of substance misuse. Converging lines of evidence motivate the hypothesis that these effects are mediated by the central extended amygdala (EAc)--including the central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST)--but the relevance of this circuitry to acute alcohol effects in humans remains poorly understood. Using a single-blind, randomized-groups design, multiband imaging data were acquired from 49 social drinkers while they performed an fMRI-optimized emotional-faces/places paradigm after consuming alcohol or placebo. Relative to placebo, alcohol significantly dampened reactivity to threat-related emotional faces in the BST. To rigorously assess potential regional differences in activation, data were extracted from anatomically defined Ce and BST regions-of-interest. Analyses revealed a similar pattern of dampening across the two regions. In short, alcohol acutely dampens reactivity to threat-related faces in humans and it does so similarly across the two major divisions of the EAc. These observations provide a framework for understanding the translational relevance of addiction models derived from work in rodents, inform on-going debates about the functional organization of the EAc, and set the stage for bi-directional translational models aimed at developing improved treatment strategies for alcohol abuse and other addictions.

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Hur, J., Kaplan, C. M., Smith, J. F., Bradford, D. E., Fox, A. S., Curtin, J. J., Shackman, A. J.. 2018-03-16. Acute alcohol administration dampens threat-related activation in the central extended amygdala. https://doi.org/10.1101/283358

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