# The Neurokinin-1 Receptor as a Mediator of Alcoholism and Depression Comorbidity

> **NIH NIH R01** · UNIVERSITY OF GEORGIA · 2024 · $363,573

## Abstract

Summary
The extended amygdala is an interconnected network of mostly limbic system structures that regulates
complex behaviors including stress responses, anxiety, social behavior, depression, and drug/alcohol seeking.
The nucleus acccumbens (NAC) and amygdala are key hubs in this network, and these regions play an
important role in integrating the effects of stress on motivated behavior. The neurokinin-1 receptor (NK1R) is
the high affinity endogenous target of the neuropeptide substance P, and the NK1R is expressed throughout
the extended amygdala, especially in the NAC and amygdala. The SP/NK1R system has been shown to
influence neurophysiological and behavioral responses to stress and drugs of abuse. During the current
funding period, we have identified a role of the NK1R in the NAC shell in the behavioral phenotypes and
escalated alcohol consumption that are induced by the major stressor of social defeat stress (SDS). We have
found that SP expressing projections to the NAC shell from the paraventricular thalamus (PVT) are activated
during SDS exposure. Interestingly, we have also observed significant SP-expressing projections from the
PVT to the central nucleus of the amygdala (CeA). Much of our prior work has focused on these two regions,
the NAC shell and the CeA, in NK1R effects on escalated alcohol consumption and stress-induced alcohol
seeking. In this renewal application, we will examine the characteristics of the PVT SP+ projections to the CeA
and NAC shell, determining how these neurons are organized anatomically and the behavioral roles played by
these discrete circuits. Additionally, we will use in vivo fiber photometry to examine the patterns of activation in
these specific circuits during alcohol consumption. Finally, since chronic alcohol exposure induces
neuroadaptations in stress-sensitive neurons, we will use translating ribosome affinity purification to isolate
mRNA transcripts that are actively translating in SP cells and will assess cell type specific alterations in PVT
gene expression following chronic alcohol exposure, determining in which SP-expressing pathways the
identified genes of interest are expressed. This will also allow for a detailed assessment of transcriptional
changes in these cells following chronic alcohol exposure, and will enable the detection of potential sex
differences. Overall, these experiments will provide valuable information on the circuit and gene expression
changes that mediate the response to alcohol, and will identify targets for the development of novel treatment
strategies.

## Key facts

- **NIH application ID:** 11000065
- **Project number:** 2R01AA026362-06A1
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** JESSE R SCHANK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $363,573
- **Award type:** 2
- **Project period:** 2018-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11000065

## Citation

> US National Institutes of Health, RePORTER application 11000065, The Neurokinin-1 Receptor as a Mediator of Alcoholism and Depression Comorbidity (2R01AA026362-06A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/11000065. Licensed CC0.

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