# Neural mechanisms underlying sustained enhancement of sociability

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $757,002

## Abstract

PROJECT SUMMARY
Social behavior comprises multiple distinct types of interactions that play a critical role in reproduction, survival,
and over-all well-being. Dysfunction of the serotonin system has long been associated with social deficits present
in a host of psychiatric and neurodevelopmental disorders, including depression, anxiety, schizophrenia, and
autism spectrum disorders. It is therefore not surprising that therapeutics targeting the serotonin system, such
as selective serotonin reuptake inhibitors (SSRIs), are commonly prescribed. Unfortunately, they are often
ineffective in improving deficits in social behavior.
Accumulating evidence supports the notion that alterations in chromatin remodelers and transcription factors
play a critical role in the development of a host of disorders. Recent findings demonstrate that selective deletion
of the chromatin remodeling subunit, Arid1b, in serotoninergic neurons results in social deficits in mice.
Interestingly, rapid elevation of serotonin levels enhances sociability and promotes appropriate social behavior.
These findings suggest that the speed and degree of serotonin enhancement is a critical regulator of its
therapeutic effects. Think of the cooling effects of using a folding fan on a humid summer day in comparison to
that of having central air conditioning on full blast. This analogy illustrates the difference in serotonin elevation
due to SSRIs versus the potent serotonin releaser MDMA, used in our studies.
Unfortunately, this effect is only temporary, and deficits resume when serotonin levels return to baseline.
However, our preliminary data suggests that a simple 2-dose MDMA regimen can cause lasting increases in
sociability in mice with this genetic deletion. The goal of this project is to identify the circuit, cellular, and molecular
adaptations underlying this potential groundbreaking therapeutic phenomenon. By studying the neural
mechanisms underlying sociability, we aim to shed light on a critically important element of the human
experience, suggesting a novel approach to effective treatments for this devastating component of many
neuropsychiatric disorders.

## Key facts

- **NIH application ID:** 10860223
- **Project number:** 1R01MH136266-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Jessica Jillian Walsh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $757,002
- **Award type:** 1
- **Project period:** 2024-03-05 → 2029-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10860223

## Citation

> US National Institutes of Health, RePORTER application 10860223, Neural mechanisms underlying sustained enhancement of sociability (1R01MH136266-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10860223. Licensed CC0.

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