# Synaptogyrin-3 promotes behavioral resilience and protects against cocaine-induced dopaminergic adaptations

> **NIH NIH F31** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Synatptogyrin-3 (SYG3) is a cocaine-sensitive synaptic vesicle protein that is yet to be fully characterized in
the context of cocaine use disorder. SYG3 is highly expressed in dopamine-containing neurons and directly
interacts with the dopamine transporter (DAT), suggesting a role in synaptic dopamine dynamics. Preliminary
studies from our laboratory suggest that cocaine breakpoint on a progressive ratio schedule of reinforcement, a
behavioral proxy for “motivation”, negatively correlates with mesolimbic SYG and DAT levels in cocaine self-
administering rats. Moreover, I found that overexpression of SYG3 in VTA dopamine neurons decreases
anxiety-like behavior and alters dopamine system function. Therefore, the objective of this proposal is to
examine the relationship between SYG3, the DAT, and cocaine self-administration. My overarching hypothesis
is that high innate levels of SYG3 induce a resilient behavioral phenotype and prevent cocaine-induced
dopamine dysfunction. I will peruse this hypothesis by answering the following 3 specific questions: (1) What
drives the inverse relationship between cocaine breakpoint and SYG3 levels? (2) Will overexpression of SYG3
in VTA dopamine neurons reduce cocaine self-administration behaviors? (3) Will overexpression of SYG3 in
VTA dopamine neurons protect against cocaine-induced dopamine dysfunction? We will pursue these aims
using both behavioral and neurochemical techniques, including affective behavioral tests, cocaine self-
administration, viral manipulations, as well as molecular and neurochemical analyses—all to determine if
SYG3 influences cocaine-taking behavior and cocaine-induced dopamine dysfunction. The proposed research
is significant, since there is no FDA approved pharmacotherapy for cocaine use disorder. The results from this
proposal will further characterize the relatively unknown synaptic vesicle protein, SYG3, as a fruitful cellular
target for pharmacotherapeutics to treat cocaine use disorder.

## Key facts

- **NIH application ID:** 10440248
- **Project number:** 5F31DA053105-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Emily Grace Peck
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 5
- **Project period:** 2021-02-16 → 2024-02-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10440248

## Citation

> US National Institutes of Health, RePORTER application 10440248, Synaptogyrin-3 promotes behavioral resilience and protects against cocaine-induced dopaminergic adaptations (5F31DA053105-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10440248. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*