# Interoceptive conditioning with nicotine: Changes in abuse liability

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA LINCOLN · 2020 · $357,244

## Abstract

PROJECT ABSTRACT
Nicotine is the primary addictive constituent in tobacco. For an individual, chronic tobacco use is associated
with a significant increase in heart disease and many forms of cancer; even the health of non-tobacco users is
negatively affected by second-hand smoke. There are some important sex differences in this addiction and its
health consequences. Women on average take less time than men to become nicotine dependent, make fewer
attempts to quit smoking, abstain for less time, relapse at higher rates, and benefit less from nicotine
replacement therapy. Clearly, enormous gains to the individual and society would come from a better
understanding of factors that contribute to nicotine dependence. Environmental stimuli associated with drugs
such as nicotine can be powerful modulators of drug-seeking behavior. Another important factor to the
development and tenacity of nicotine dependence is the pharmacological effects of nicotine serving as an
interoceptive (internal) stimulus entering into a conditioned association with other reinforcers/unconditioned
stimuli [USs (peer acceptance, alcohol, work breaks, stress relief)]. Consequently, over time, a smoker has an
opportunity to develop a rich appetitive conditioning history with the stimulus effects of nicotine. This acquired
reinforcing value likely contributes to the tenacity of the nicotine addiction. Using a newly developed
preclinical animal model that innovatively merges interoceptive conditioning with nicotine self-administration,
the present application will rigorously test the hypothesis that following an appetitive interoceptive
conditioning history with nicotine, the nicotine stimulus will acquire conditioned reinforcing value that
exacerbates the persistence of nicotine-taking behavior. To this end, the Specific Aims will examine how such
enhancement of drug intake varies with the salience (dose) of the nicotine stimulus (Aim 1), assess the synergy
between nicotine and ethanol by using ethanol or sucrose-ethanol solution as the US (Aim 2), and implement
an innovative extinction protocol designed to weaken the acquired conditioned reinforcing value of nicotine to
a greater extent than just simple non-reinforcement of the target stimulus (Aim 3) in female and male rats.

## Key facts

- **NIH application ID:** 9929569
- **Project number:** 5R01DA046109-03
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** Rick A Bevins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $357,244
- **Award type:** 5
- **Project period:** 2018-07-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9929569

## Citation

> US National Institutes of Health, RePORTER application 9929569, Interoceptive conditioning with nicotine: Changes in abuse liability (5R01DA046109-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9929569. Licensed CC0.

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