# The role of serotonin signaling in the nucleus accumbens in excessive alcohol drinking

> **NIH NIH R00** · UNIVERSITY OF IOWA · 2020 · $280,799

## Abstract

PROJECT SUMMARY/ABSTRACT
Alzheimer's disease (AD) is a significant public health problem that afflicts approximately 10% of those ages 65
and over. Tremendous efforts have been dedicated toward understanding the mechanisms of cognitive decline,
but few studies have focused on the early non-cognitive symptoms of AD. Several lines of evidence indicate that
depressive symptoms precede the development of cognitive decline, but the underlying circuits are poorly
understood. Earlier studies have found that dynorphin is overexpressed in the brains of AD patients, which may
induce deficits in dopamine signaling that can lead to anhedonia. We have previously found that stimulating
dynorphin neurons in the nucleus accumbens induces depressive-like behaviors in mice, so we asked whether
dynorphin signaling in the NAcc was enhanced in mice expressing human tau pathology (htau mice). We also
have data suggesting that NAcc dynorphin neurons inhibit local dopamine release, which we expect to be
potentiated in htau mice. Recent studies also suggest that heavy alcohol use may worsen tau pathology
associated with AD. Our lab has also shown that chronic alcohol use heightens activity in NAcc dynorphin
neurons, raising the possibility that alcohol may act in synergy with tau to promote depressive-like behaviors.
We will determine whether chronic ethanol exacerbates tau pathology in NAcc dynorphin neurons and whether
enhanced neural activity in these neurons plays a role in this process. Together, these experiments will reveal
neural mechanisms underpinning the early non-cognitive symptoms of AD and the role of chronic alcohol in
facilitating the progression of AD.

## Key facts

- **NIH application ID:** 10123843
- **Project number:** 3R00AA024215-04S1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Catherine Anne Marcinkiewcz
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $280,799
- **Award type:** 3
- **Project period:** 2017-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123843

## Citation

> US National Institutes of Health, RePORTER application 10123843, The role of serotonin signaling in the nucleus accumbens in excessive alcohol drinking (3R00AA024215-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10123843. Licensed CC0.

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