# Prenatal Ethanol Exposure and Nitric Oxide Signaling in Serotonin Neurons

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2020 · $358,875

## Abstract

Project Summary
Prenatal ethanol exposure (PE) causes fetal alcohol spectrum disorders (FASD), which is characterized by
severe cognitive, motor deficits and mood disorders including, major anxiety disorder. FASD affects up to 5%
of children and exerts a devastating burden on families, individuals and costs to the society making it one of
the most significant health problems in the USA and worldwide. Currently, effective treatments of FASD are
limited, which underscores the need for a better understanding of the neuronal mechanisms underpinning the
behavioral deficits associated with FASD. Research conducted over the last decades has established that PE
impairs the development and function of serotonin (5-HT) system. Although it is widely recognized that
dysfunctions of the serotonin (5-HT) system play a major role in depression and major anxiety disorders
associated with FASD, the mechanisms by which PE alters the function of dorsal raphe (DRn) 5-HT neurons
and the precise 5-HT networks affected remain unknown. To address these important knowledge gaps, we
have examined the impact of PE on the function of dorsal raphe (DRn) 5-HT neurons. The results of these
studies have established that PE, which induces anxiety phenotype, profoundly, increases the activity of DRn
5-HT neurons, via a persistent potentiation of glutamatergic transmission in the DRn. Importantly, a novel
finding of our preliminary mechanistic studies is that these effects are mediated by enhanced nitric oxide (NO)
signaling. In this application, we will build on this progress and test the novel hypothesis that enhanced
nitrergic function in PE rats mediates the potentiation of glutamatergic transmission onto DRn 5-HT neurons,
identify the subset(s) of 5-HT projecting neurons affected, and dissect the neuronal networks mediating anxiety
phenotype of PE rats. In Aim 1, we will test the hypothesis that enhanced NO signaling mediates the
potentiation of glutamate synapses in the DRn, and identify the subset(s) of DRn 5-HT projecting neurons
affected. In Aim 2, we will dissect the glutamatergic input(s) to DRn 5-HT neurons altered in PE rats. In Aim 3,
we will test whether reducing specific glutamatergic inputs to DRn 5-HT neurons alleviates anxiety in PE rats.
This multidisciplinary approach will identify the cellular mechanisms mediating the dysfunction of 5-HT system
and define the neuronal circuitries underlying anxiety phenotype of PE rats. The outcome of these experiments
will also lay the foundation for future studies aiming at developing effective therapy of mood disorders
associated with FASD.

## Key facts

- **NIH application ID:** 9990640
- **Project number:** 5R01AA026601-03
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** SAMIR HAJ-DAHMANE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $358,875
- **Award type:** 5
- **Project period:** 2018-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990640

## Citation

> US National Institutes of Health, RePORTER application 9990640, Prenatal Ethanol Exposure and Nitric Oxide Signaling in Serotonin Neurons (5R01AA026601-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9990640. Licensed CC0.

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