# Sex differences in the neurochemical mechanisms by which a stress peptide enhances nicotine reward and withdrawal

> **NIH NIH F31** · UNIVERSITY OF TEXAS EL PASO · 2020 · $18,474

## Abstract

Project Abstract
 Tobacco use remains a major public health problem, particularly in women who are more vulnerable to
the long-term consequences of smoking. Unfortunately, there is a critical knowledge gap regarding the
underlying mechanisms by which stress promotes the behavioral effects of nicotine in females. The objective of
this fellowship application is to investigate the role of stress systems in promoting nicotine reward and withdrawal
in female rats. Our central hypothesis is that sex differences in the behavioral effects of nicotine are modulated
via stress systems in the local circuits of the nucleus accumbens (NAc), a terminal region of the mesolimbic
dopamine pathway. The rationale for our hypothesis is based on our preliminary studies showing that viral-
mediated over-expression of corticotrophin-releasing factor (CRF) in the NAc selectively enhances the rewarding
effects of nicotine in female versus male rats. Our mechanistic hypothesis is that sex differences in the behavioral
effects of nicotine are modulated via inhibitory (GABA) and excitatory (glutamate) amino acids that regulate
dopamine release in the NAc. Thus, the proposed studies will examine sex differences in the neurochemical
effects of nicotine in female and male rats that received over-expression of CRF in the NAc (Aim 1). We predict
that activation of CRF1 receptors following CRF over-expression produces a decrease in GABA transmission
that results in enhanced dopamine release in the NAc of female versus male rats. We will examine whether
these effects are CRF1 receptor mediated by infusing the CRF1 receptor antagonist, antalarmin into the NAc
during our dialysate collections. Subsequent studies will examine sex differences in the neurochemical effects
of nicotine withdrawal in female and male rats that received over-expression of CRF in the NAc (Aim 2). We
predict that CRF over-expression will exacerbate the neurochemical effects of nicotine withdrawal via the
emergence of large increases in glutamate release onto GABAergic interneurons. We expect that this effect will
lead to a larger increase in GABA release that will contribute to a larger decrease in NAc dopamine release in
female versus male rats. The project will provide important information regarding the role of stress systems in
the behavioral effects of nicotine.

## Key facts

- **NIH application ID:** 9928293
- **Project number:** 5F31DA046126-02
- **Recipient organization:** UNIVERSITY OF TEXAS EL PASO
- **Principal Investigator:** Kevin Patrick Uribe
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $18,474
- **Award type:** 5
- **Project period:** 2019-01-10 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928293

## Citation

> US National Institutes of Health, RePORTER application 9928293, Sex differences in the neurochemical mechanisms by which a stress peptide enhances nicotine reward and withdrawal (5F31DA046126-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9928293. Licensed CC0.

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