# Targeting Neurokinin Receptors to Regulate of Nicotine Reward

> **NIH NIH U54** · XAVIER UNIVERSITY OF LOUISIANA · 2021 · $75,000

## Abstract

Title: Targeting Neurokinin Receptors to Regulate of Nicotine Reward
Abstract
Current FDA approved treatments are not sufficient to promote nicotine cessation in all individuals, highlighting
the need for novel drug targets. Several studies have highlighted the role of α5-containing (α5*) nicotinic
acetylcholine receptors (nAChRs) in the modulation of both nicotine intake and the emergence of nicotine
withdrawal-associated behaviors. To date there are no α5 nAChR selective drugs available for human use.
Another approach to probe the potential therapeutic effects of α5* nAChRs is to target other neurotransmitter
systems that directly interacts with α5 nAChR signaling pathways in the brain. One such system is the
neurokinin signaling pathway. Previous research conducted by my colleagues and I have demonstrated a
direct interaction between α5* nAChRs and neurokinin 1 receptors (NK1Rs) in modulating the neuronal
response to nicotine and the emergence of physical signs of nicotine withdrawal. The goal of this proposal is to
gather preliminary data to characterize the role that NKRs play on nicotine-induced behaviors and their
interaction with α5* nAChRs.
Aim 1 of the proposal will address the hypothesis that selective antagonism of NK1Rs will alter the rewarding
effects of nicotine in wild type mice. We will use behavioral tests such as conditioned place preference and
operant self-administration of nicotine vapor to measure the influence that NK1Rs have on nicotine-induced
rewarding effects. We will also use in vivo microdialysis to measure nicotine-induced dopamine release in the
nucleus accumbens. Specific aim 2 will address the hypothesis that NKRs interact with α5* nAChRs to mediate
nicotine reward associated behaviors. α5 null mice have altered nicotine reward behaviors such as enhanced
nicotine consumption and altered nicotine-induced dopamine release. Given our previous data suggesting a
direct interaction between these two receptor systems, we predict that direct stimulation of NK1Rs will
normalized dopamine release within the nucleus accumbens. Moreover this aim will collect preliminary data to
test whether antagonism of NK1Rs will normalize nicotine consumption in α5 null mice.
This proposal will allow for the collection of preliminary data to be used in the preparation of a SURE-First R16
Award. We have evidence that both NK1Rs modulate nicotine activity via interaction with α5* nAChRs,
therefore; we do expect to see significant changes in nicotine-induced rewarding behaviors. Future studies will
on understanding the specific mechanism in which NKRs and α5* nAChRs modulate drug-induced behaviors.

## Key facts

- **NIH application ID:** 10430774
- **Project number:** 3U54MD007595-13S4
- **Recipient organization:** XAVIER UNIVERSITY OF LOUISIANA
- **Principal Investigator:** Gene D'Amour
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $75,000
- **Award type:** 3
- **Project period:** 2009-09-24 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10430774

## Citation

> US National Institutes of Health, RePORTER application 10430774, Targeting Neurokinin Receptors to Regulate of Nicotine Reward (3U54MD007595-13S4). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10430774. Licensed CC0.

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