# Alcohol-induced alterations in orbitofrontal cortex serotonin signaling

> **NIH NIH K99** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $126,357

## Abstract

Project Summary
Excessive alcohol consumption is a leading cause of mortality and economic burden in the United States. Of
the patterns of excessive intake, binge drinking is the most common and accounts for approximately half of the
deaths attributable to alcohol. In addition to high rates of mortality, repeated cycles of binge alcohol intake and
withdrawal cause persistent adaptations in brain regions that increase the risk of psychiatric symptoms and
subsequent excessive alcohol consumption. This places individuals at greater risk for developing alcohol
dependence. These outcomes may be driven by dysregulation in serotonin (5-hydroxytryptamine, 5-HT)
systems originating in the dorsal raphe nucleus (DR). Although involvement of 5-HT has been well established
in alcohol use disorder, we lack a thorough understanding of the neural circuits and precise signaling
mechanisms that underlie this dysregulation. In this proposal, I will examine the adaptations in a 5-HT circuit
from the DR to the orbitofrontal cortex (OFC) that result from repeated episodes of binge-like alcohol intake. I
will accomplish this using a series of converging and highly innovative ex vivo and in vivo techniques that will
allow me to measure binge alcohol-induced changes in 5-HT release and signaling dynamics in the DR and
the OFC. Further, I will probe the causal role of 5-HT signaling in the DR-OFC circuit in promoting excessive
alcohol intake. In addition to providing me with advanced technical training and professional development
activities, this proposal will provide essential information concerning the actions of binge-like alcohol drinking
on 5-HT neural circuitry and signaling. Ultimately, this proposal will identify a circuit-based signaling
mechanism that can be used for the targeted treatment of alcohol use disorder.
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## Key facts

- **NIH application ID:** 9952589
- **Project number:** 1K99AA028298-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Melanie M Pina
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $126,357
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9952589

## Citation

> US National Institutes of Health, RePORTER application 9952589, Alcohol-induced alterations in orbitofrontal cortex serotonin signaling (1K99AA028298-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9952589. Licensed CC0.

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