# Alcohol-Induced Alterations in Orbitofrontal Cortex Serotonin Signaling

> **NIH NIH R00** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $76,809

## Abstract

Project Summary
Repeated episodes of binge alcohol drinking dysregulate serotonin (5-hydroxytryptamine, 5-HT) systems
throughout the brain, which may place an individual at greater risk of developing an alcohol use disorder
(AUD). The orbitofrontal cortex (OFC) is one site of 5-HT innervation that has been shown to undergo plastic
changes after heavy alcohol intake. Previous work has indicated that chronic alcohol exposure disrupts 5-HT
signaling in the OFC, leading to a loss of its inhibitory control in this region. Preliminary findings from the
parent R00 grant show that binge-like patterns of alcohol intake alter OFC activity across multiple species
and produce profound impairments in 5-HT1A receptor signaling in this region. However, this work from our
group and others has focused primarily on pyramidal neurons when evaluating alcohol’s impact on the OFC.
Of note, the OFC has a complex microcircuitry that contains interspersed GABA interneurons (INs) that fine-
tune the activity patterns of pyramidal cells and other IN populations. These cortical INs, which can be
broadly classified based on their expression of parvalbumin (PV) or somatostatin (SST), appear to serve
distinct roles in the coordination of OFC activity. Given the complex microcircuitry of the OFC and interplay
between its mixed neuronal populations, it will be informative to examine the broader cellular network in
which alcohol-induced adaptations may occur. At present, the impact of binge intake on OFC PV-INs and
SST-INs remains unknown. The project proposed by the supplement candidate will address this knowledge
gap through a series of experiments that evaluate plasticity induced by binge-like alcohol drinking in PV-INs
and SST-INs and its effect on 5-HT signaling in these cell populations. In Aim 1, the candidate will perform
whole-cell patch clamp electrophysiology recordings in the OFC of PV and SST reporter mice following
repeated cycles of binge alcohol intake. Specifically, the candidate will examine changes in excitability,
synaptic transmission, and 5-HT signaling in these genetically defined IN populations. In Aim 2, the applicant
will use fluorescence in situ hybridization to measure the effect of binge alcohol on 5-HT receptor mRNA
expression levels in OFC PV and SST INs. In addition to yielding novel information, this supplement award
will add to the candidate’s existing scientific toolkit by allowing him to receive training in more advanced
cellular and molecular techniques, including ex vivo electrophysiology, fluorescence in situ hybridization, and
confocal microscopy. Beyond technical training, this diversity supplement will provide the candidate with
professional development opportunities and an individualized mentoring plan that will support his graduate
work and foster his career progression. Combined, the proposed project and supplemental training will
enhance the candidate’s graduate research experience and facilitate his successful transition to the next
...

## Key facts

- **NIH application ID:** 10975735
- **Project number:** 3R00AA028298-05S1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Melanie M Pina
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,809
- **Award type:** 3
- **Project period:** 2022-01-03 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10975735

## Citation

> US National Institutes of Health, RePORTER application 10975735, Alcohol-Induced Alterations in Orbitofrontal Cortex Serotonin Signaling (3R00AA028298-05S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10975735. Licensed CC0.

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