# Understanding and mitigating exacerbated nicotine use resulting from Pavlovianinteroceptive conditioning

> **NIH DA R01** · UNIVERSITY OF NEBRASKA LINCOLN · 2026 · $359,776

## 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. Increasingly, researchers are documenting
health issues associated with vaping flavored e-juice containing nicotine. There are some important sex
differences in chronic nicotine use and its health consequences. Women on average are impacted more by
environmental and sociocultural factors, take less time to become nicotine dependent, make fewer attempts to
quit, abstain for less time, relapse at higher rates, and benefit less from nicotine replacement therapy. Enormous
gains to the individual and society would come from a more complete understanding of factors that contribute
to nicotine use and misuse. Through Pavlovian conditioning processes, environmental stimuli associated with
drugs such as nicotine can become powerful modulators of drug-seeking behavior. Another related and
important factor in the development of chronic nicotine use is the pharmacological effects of nicotine serving as
an internal (interoceptive) stimulus that enters into a conditioned association with other reinforcers (e.g., peer
acceptance, alcohol, work breaks, stress relief, etc.). Thus, smokers/vapers over time develop a rich interoceptive
conditioning history with the stimulus effects of nicotine. Our long-term objective is to understand how this
conditioning history alters the trajectory of use and misuse in individuals and, in doing so, provide new clues on
how to improve cessation programs. To this end, we recently developed an innovative new approach using rats
that merges interoceptive conditioning of intravenous (IV) nicotine with its later self-administration. When IV
nicotine is repeatedly paired with an appetitive reinforcer (i.e., sucrose), this conditioning history dose- and sex-
dependently increases nicotine self-administration (21 to 126%)—an effect more profound in female rats.

## Key facts

- **NIH application ID:** 11319896
- **Project number:** 5R01DA057208-04
- **Recipient organization:** UNIVERSITY OF NEBRASKA LINCOLN
- **Principal Investigator:** Rick A Bevins
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** DA
- **Fiscal year:** 2026
- **Award amount:** $359,776
- **Award type:** 5
- **Project period:** 2023-07-01T00:00:00 → 2028-04-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11319896

## Citation

> US National Institutes of Health, RePORTER application 11319896, Understanding and mitigating exacerbated nicotine use resulting from Pavlovianinteroceptive conditioning (5R01DA057208-04). Retrieved via AI Analytics 2026-06-26 from https://api.ai-analytics.org/grant/nih/11319896. Licensed CC0.

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