Acute alcohol administration dampens central extended amygdala reactivity

Juyoen Hur,Jason F Smith,Alexander J Shackman,Andrew S Fox,Claire M Kaplan,Daniel E Bradford,John J Curtin

doi:10.1038/s41598-018-34987-3

Abstract

Alcohol use is common, imposes a staggering burden on public health, and often resists treatment. The central extended amygdala (EAc)—including the bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce)—plays a key role in prominent neuroscientific models of alcohol drinking, but the relevance of these regions to acute alcohol consumption in humans remains poorly understood. Using a single-blind, randomized-groups design, multiband fMRI data were acquired from 49 social drinkers while they performed a well-established emotional faces paradigm after consuming either alcohol or placebo. Relative to placebo, alcohol significantly dampened reactivity to emotional faces in the BST. To rigorously assess potential regional differences in activation, data were extracted from unbiased, anatomically predefined regions of interest. Analyses revealed similar levels of dampening in the BST and Ce. In short, alcohol transiently reduces reactivity to emotional faces and it does so similarly across the two major divisions of the human EAc. These observations reinforce the translational relevance of addiction models derived from preclinical work in rodents and provide new insights into the neural systems most relevant to the consumption of alcohol and to the initial development of alcohol abuse in humans.

Highlights

Alcohol use is common, contributes to a variety of adverse outcomes, and imposes a rapidly growing burden on public health and the economy[1,2,3], highlighting the need to understand the acute impact of alcohol consumption on the human brain
Evidence gleaned from animal models highlights the potential importance of the central extended amygdala (EAc), including the bed nucleus of the stria terminalis (BST) and the central nucleus of the amygdala (Ce)[4,5] (Fig. 1)
The EAc plays a key role in prominent neuroscientific models of alcohol-drinking[14,15,16,17,18], with work in rodents indicating that alcohol acutely dampens EAc reactivity[19,20,21,22,23]

Summary

Introduction

Alcohol use is common (nearly three-quarters of Americans consumed some form of ethanol in the past year and, among them, 17.5% met criteria for an alcohol use disorder), contributes to a variety of adverse outcomes, and imposes a rapidly growing burden on public health and the economy[1,2,3], highlighting the need to understand the acute impact of alcohol consumption on the human brain. Was rooted in work demonstrating that the amygdala is robustly activated by emotional faces, those depicting expressions of fear[28,29,30,31] This has motivated the use of similar paradigms in work focused on the development of anxiety and mood disorders[32,33] and the acute impact of alcohol and pharmaceutical (e.g. benzodiazepine) interventions[24,25,26,27,34,35], as well as large-scale neuroimaging initiatives (e.g., Human Connectome Project, UK BioBank)[36,37]. Understanding the acute consequences of alcohol for EAc function is important It would clarify whether models of substance abuse derived from work in rodents—a species that diverged from the ancestors of modern humans ~75 million years ago41—are relevant to human alcohol consumption[14,15]. It promises to inform our understanding of work linking variation in EAc function to the emergence of alcohol abuse[42,43] and to provide insight into the EAc’s role in recreational drinking

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