# Structural and functional responses of nucleus accumbens microglia following long-access cocaine self-administration

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $40,441

## Abstract

ABSTRACT
Cocaine use disorder (CUD) is a persistent public health concern in the United States, exacerbated by the
coronavirus-19 pandemic. Moreover, the only treatment for CUD is behavioral therapy, as there are currently
no FDA-approved pharmaceutical therapeutics for CUD. This poses a concern, as individuals experiencing
CUD are at substantial risk for relapse across abstinence. A deeper understanding of the cellular and
molecular underpinnings of CUD is essential for developing therapeutics and relapse prevention for
sustainable abstinence. Although extensive research to date has focused primarily on neuronal mechanisms of
cocaine action in the brain, available evidence indicates that neuroglia may significantly contribute to
mechanisms of dependence and relapse. The Reissner Lab focuses heavily on understanding the role of
astrocytes and microglia in the maintenance of cocaine use disorder and relapse-like behaviors. Published
research from the Reissner lab illustrates substantial morphological decreases in the nucleus accumbens core
astrocytes following long-access (LgA, 6 h/day, 10 days) cocaine self-administration and a 45-day abstinence
period. Preliminary data for this proposal show a significant effect of cocaine and abstinence on the
colocalization of astrocyte membranes within microglia, suggesting that microglia may be mediating the effect
of cocaine on astrocytes and raising the possibility that microglia phagocytosis is a long-lasting consequence
of cocaine use. Thus, this proposal aims to investigate how structural and functional microglial responses in
the nucleus accumbens contribute to cocaine dependence and relapse behaviors. In Aim 1, I will explore
morphological responses of accumbens microglial, in addition to evidence of engulfment of astrocyte
membranes, across abstinence in males and females. In Aim 2, I will test the hypothesis that pharmacological
inhibition of microglial phagocytosis will protect against the effects of cocaine on astrocyte structure, microglial
engulfment of astrocytes, and cocaine-seeking behavior. A neutrophil inhibitory factor (NIF) peptide which
inhibits the protein interaction between complement protein C3 and the microglial C3 receptors will be directly
microinjected into the nucleus accumbens, inhibiting phagocytosis. Additionally, this aim will explore the source
of phagocytosis signaling by examining “eat me”/“don’t eat me” signals such as C3 colocalization with
astrocytes and synapses. The experiments proposed in Aim 3 will characterize the genetic profiles of microglial
cells following long-access cocaine self-administration. Through the use of magnetic bead sorting and RT-
qPCR, I will be able to identify expression changes of microglia-specific genes. Overall, the findings of this
study will provide a foundation for understanding how microglial morphological and functional responses
contribute to cocaine dependence in both male and female rats. Further, insights into the role microglia p...

## Key facts

- **NIH application ID:** 10903218
- **Project number:** 1F31DA060688-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Tania Jazmine Bellinger
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,441
- **Award type:** 1
- **Project period:** 2024-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10903218

## Citation

> US National Institutes of Health, RePORTER application 10903218, Structural and functional responses of nucleus accumbens microglia following long-access cocaine self-administration (1F31DA060688-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10903218. Licensed CC0.

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