# Border Biomedical Research Center Administrative Supplement

> **NIH NIH U54** · UNIVERSITY OF TEXAS EL PASO · 2022 · $228,000

## Abstract

Abstract
The goal of the Border Biomedical Research Center (BBRC) is to provide an infrastructure to study the factors
that promote cancer-related health disparities, including nicotine use. The proposed administrative supplement
will enhance research capacity by integrating a team of scientists that are focused on the mechanisms by which
stress promotes nicotine use and subsequent increased risk of cancer. Recently, we discovered important new
insights into the mechanisms by which stress systems in the habenula-interpeduncular nucleus (Hb-IPN)
pathway modulate sex differences in nicotine withdrawal. Specifically, we found that withdrawal severity is
closely associated with the activation of interneurons in the IPN that release the inhibitory neurotransmitter,
gamma aminobutyric acid (GABA). This work established that inhibitory tone in the IPN plays a key role in the
behavioral effects of nicotine withdrawal. The primary objective of this application is to vertically extend our prior
work by determining the mechanisms by which stress systems in the IPN modulate withdrawal from chronic
nicotine vapor inhalation. Our central hypothesis is that stress enhances anxiety-like behavior during withdrawal
to a larger extent in females versus males, and this effect is due to greater inhibitory tone in the IPN. We expect
that the proposed work will lead to a stronger mechanistic foundation for understanding how stress systems are
anatomically positioned to increase inhibitory tone in the IPN during withdrawal in female versus male rats. A
secondary objective is to assess changes in plasma biomarkers levels from rats that were included in the
mechanistic studies of Aim 1. We will assess the relationship between stress, nicotine use, and subsequent
biomarkers of allostatic load. We hypothesize that stress and high levels of nicotine intake in females will increase
the biomarkers of allostatic overload versus males. The successful completion of the proposed work is likely to
contribute to a mechanistic framework for the development of new nicotine use cessation strategies, particularly
for women. The proposed work capitalizes upon BBRC core facilities to attain our objectives in two specific aims.
Aim 1 will elucidate the mechanisms that modulate sex differences in nicotine withdrawal. Our working
hypothesis is that exposure to a variable stress regimen will enhance nicotine withdrawal severity in females via
greater inhibitory tone in the IPN as compared to males. Aim 2 will examine the relationship between chronic
stress and nicotine exposure on allostatic overload and subsequent changes in the biomarkers of cancer risk.
Our working hypothesis is that stress and nicotine exposure in females will produce greater allostatic overload
as compared to males. At the completion of the proposed work, our expected outcomes are to have 1) defined
the mechanisms of sex differences in nicotine withdrawal and 2) explored sex differences in the influence of
chronic stress...

## Key facts

- **NIH application ID:** 10489606
- **Project number:** 3U54MD007592-29S3
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Robert A. Kirken
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $228,000
- **Award type:** 3
- **Project period:** 1998-06-15 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489606

## Citation

> US National Institutes of Health, RePORTER application 10489606, Border Biomedical Research Center Administrative Supplement (3U54MD007592-29S3). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10489606. Licensed CC0.

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