The study design consists of a randomized, double-blind, placebo-controlled trial of low dose
endotoxin. The low dose endotoxin challenge induces a transient systemic inflammatory
response with normalization of cytokine levels within hours. This "phasic" inflammation is
distinct from chronic ("tonic") levels of inflammation that may be present with AUD. A total
of 38 non-treatment seeking heavy drinking men and women and 38 light drinking healthy
controls will participate in the study. Recruitment will be monitored to ensure the two
groups are matched by gender. Eligible participants will be randomly assigned, stratified by
gender and BDI-II severity, to receive a single I.V. infusion of either low dose endotoxin
(0.8 ng/kg of body weight) or placebo (same volume of 0.9% saline solution) at the UCLA
Outpatient Clinical and Translational Research Center (CTRC). All participants will complete
an alcohol cue-exposure paradigm and reward responsiveness assessment 2 hours post infusion,
which is the time of expected peak cytokine response. All participants will also complete an
fMRI alcohol cue-reactivity paradigm at 3 hours post infusion. Plasma levels of
proinflammatory cytokines [i.e., Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF- α)],
mood, and alcohol craving, will be assessed at baseline and then hourly for four hours post
infusion.