# Does endotoxin administration increase alcohol consumption in individuals with AUD?

> **NIH NIH R03** · YALE UNIVERSITY · 2021 · $83,750

## Abstract

PROJECT SUMMARY
This NIH Small Research Grant Program (Parent R03) application proposes support for early stage
investigator Terril Verplaetse, Ph.D., to establish a new research program in the area of neuroinflammation and
alcohol research. Neuroimmune function is a key system linked to negative reinforcement drinking and to the
development of alcohol use disorder (AUD). Stress and chronic alcohol consumption have been found to
increase microglial activity, a marker of neuroinflammation. However, the role of neuroinflammation on alcohol
use behavior is less clear. Endotoxin, also called lipopolysaccharide (LPS), is well-known to induce
neuroinflammation and acute stress. In preclinical studies, LPS increases voluntary ethanol intake. {{{To our
knowledge, a provocation study to examine neuroinflammation-induced drinking has not been developed in
humans with AUD.}}}. Further, rates of AUD have increased in women by 84% over the past ten years relative
to a 35% increase in men. Stress and greater neuroimmune response are associated with alcohol use for both
women and men but play an especially critical role in women. Thus, this application will generate data to
calculate effect sizes for the interaction between sex and endotoxin (vs. placebo) administration on drinking
behavior and potential mechanisms underlying endotoxin effects on drinking in women vs. men. The goal of
this proposed research is to examine the role of neuroinflammation on acute drinking in women and men and
to investigate sex differences in potential mechanisms underlying the role of neuroinflammation on alcohol self-
administration. The study population will be individuals meeting DSM-5 criteria for AUD. This project features a
well-validated human laboratory paradigm that models two critical features of drinking behavior; the ability to
resist drinking (i.e., reducing time to initiate drinking) and subsequent ad-libitum drinking (i.e., milliliters of
alcohol consumed). To determine whether endotoxin (vs. placebo) increases our primary outcomes of time to
initiate drinking and amount of alcohol consumed in women and men, individuals will complete a single
laboratory session in which LPS (vs. placebo; {{{double-blinded}}}) is administered prior to a 2-hour alcohol
self-administration session (Specific Aim 1). We will also evaluate the safety of endotoxin in combination with
alcohol in individuals with AUD (Specific Aim 2). Additional analyses will examine potential sex differences in
mechanisms underlying endotoxin (vs. placebo) effects on drinking behavior (e.g., peripheral cytokines,
craving, subjective intoxication, mood, stress, heart rate, blood pressure, cortisol, ACTH, {{{and sex
hormones}}}) over the course of the 2-hour alcohol self-administration session (Specific Aim 3). Taken
together, this proposal will provide valuable data for evaluating the role of neuroinflammation on alcohol-
motivated behavior and will have abundant applications to inform novel pharmacotherapeu...

## Key facts

- **NIH application ID:** 10118646
- **Project number:** 1R03AA028361-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Terril L Verplaetse
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $83,750
- **Award type:** 1
- **Project period:** 2021-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10118646

## Citation

> US National Institutes of Health, RePORTER application 10118646, Does endotoxin administration increase alcohol consumption in individuals with AUD? (1R03AA028361-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10118646. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*