# Neurobehavioral mechanisms linking childhood adversity to increased risk for smoking

> **NIH NIH R01** · DUKE UNIVERSITY · 2022 · $595,710

## Abstract

Adverse childhood experiences (ACEs) have been linked to increased risk of tobacco use and
other substance use disorders. In particular, individuals with a higher number of ACEs are more
likely to smoke cigarettes, initiate smoking at earlier ages, progress to heavier smoking, have
higher levels of dependence, and are less likely to quit. However, very few human laboratory
studies have been conducted to examine interactions between ACEs and risk for smoking, and
the mechanisms underlying these associations are poorly understood. Based on several
converging lines of evidence, we propose a translational framework in which ACEs are
associated with alterations in corticostriatal circuitry contributing to dysregulated reward
processing, which in turn increases sensitivity to reinforcing effects of drugs of abuse, including
nicotine. The proposed research will apply a laboratory model of initial nicotine exposure using
nasal spray to examine subjective reactions and reinforcing effects of nicotine among young
adult non-smokers (n=150) with a history of ACEs ranging from 0 to 4 or more. Participants will
first complete a functional neuroimaging protocol designed to assess mesolimbic reactivity to
monetary reward, prefrontal inhibitory control, and corticostriatal functional connectivity.
Subjective reactions to 0, .5, or 1 mg doses of nicotine nasal spray will be assessed during
three separate fixed-dose visits. We will then evaluate reinforcing effects of nicotine during a
choice session. In general, we hypothesize that increased exposure to ACEs will be associated
with greater positive subjective and reinforcing effects of nicotine, that deficits in corticostriatal
circuitry will mediate the association between ACEs and nicotine reactions, and that this
association will be stronger among women. These results will provide a critical translation from
animal models demonstrating consequences of early life stress on neurobiological pathways
relevant to addiction. Moreover, this work will help to explain the increased risk for smoking
among individuals exposed to ACEs and will have implications for prevention and treatment of
smoking in this high-risk population and beyond.

## Key facts

- **NIH application ID:** 10521541
- **Project number:** 1R01DA054972-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Maggie M Sweitzer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $595,710
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10521541

## Citation

> US National Institutes of Health, RePORTER application 10521541, Neurobehavioral mechanisms linking childhood adversity to increased risk for smoking (1R01DA054972-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10521541. Licensed CC0.

---

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