# Impact of electronic nicotine vapor on mouse mesolimbic CRFR1 circuitry and motivated behavior

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $39,251

## Abstract

PROJECT SUMMARY/ABSTRACT
Nicotine is a highly addictive substance found in cigarettes as well as in electronic nicotine vapor products.
More recently, nicotine delivered through electronic vapor systems have grown in popularity, especially in the
adolescent population. Although these products are often marketed as safer alternatives, the effects of
electronically delivered nicotine vapor exposure on the brain and behavior, remain understudied. Nicotine
activates the brain reward pathway which mainly consists of dopaminergic neurons in the ventral tegmental
area (VTA) that sends projections and release dopamine (DA) into the nucleus accumbens (NAc). The VTA is
a heterogenous neuron population, including dopaminergic, glutamatergic, and GABAergic neurons that can
interact to differentially modulate reward signaling. Nicotine also plays an important role in modulating stress
and anxiety behaviors which in turn can exacerbate nicotine addiction. A principal component of central and
peripheral stress regulation is the corticotropin-releasing factor (CRF) system. The CRF neuropeptide binds
primarily to corticotropin-releasing factor 1 receptors (CRFR1) in the brain which are expressed in VTA
neurons. However, the role of VTA CRFR1 neurons in the reward pathway and the impact of nicotine vapor
exposure on reward signaling, remain unclear. To investigate the VTA CRFR1 population and its role in
nicotine effects on the reward pathway, I will use a transgenic mouse model expressing green fluorescent
protein under the CRFR1 promoter (CRFR1-GFP). I will characterize the cell types, projections,
electrophysiological properties, and sensitivity to cellular nicotine application of VTA CRFR1 neurons to
establish foundational information in naïve male and female animals (Aim 1). Using a rodent electronic nicotine
vapor system, I will expose male and female mice acutely and chronically to nicotine vapor and examine the
changes in neuronal activity and electrophysiological properties of VTA CRFR1 neurons (Aim 2). Additionally, I
will examine motivated behavior using self-administration of electronic nicotine vapor in different reward
conditions (increasing effort or decreasing reward value, Aim3). My overarching hypothesis is that CRFR1
neurons in the VTA are involved in the mesolimbic reward circuitry and that exposure to chronic electronic
nicotine vapor will alter basal electrophysiological properties and sensitivity to cellular nicotine, leading to
maladaptive behaviors. Together, the proposed experiments will reveal how acute and chronic electronic
nicotine vapor exposure can alter a stress-sensitive component of the mesolimbic reward circuit and contribute
to maladaptive behaviors like drug self-administration. Understanding the mechanisms that integrate stress
and reward in the context of nicotine addiction can better inform policies that regulate the availability of nicotine
vapor products and potentially identify cellular targets for therapeutics.

## Key facts

- **NIH application ID:** 10151988
- **Project number:** 1F31DA053064-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** ManHua Zhu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $39,251
- **Award type:** 1
- **Project period:** 2021-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151988

## Citation

> US National Institutes of Health, RePORTER application 10151988, Impact of electronic nicotine vapor on mouse mesolimbic CRFR1 circuitry and motivated behavior (1F31DA053064-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10151988. Licensed CC0.

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