# Investigating cytoskeletal dynamics in astrocyte structure and cocaine seeking behavior

> **NIH NIH F31** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 · $38,617

## Abstract

ABSTRACT
Cocaine abuse presents a significant public health concern across the United States, as the number of
cocaine-related deaths in the United States has almost tripled since 2013. Despite an urgent need for
intervention, an FDA-approved treatment for Cocaine Use Disorder is lacking. Hence, there is a considerable
need for investigations into the mechanisms that drive relapse vulnerability. Recent advances indicate that
cocaine-induced structural adaptations in astrocytes may contribute to relapse vulnerability. Astrocytes are the
most abundant glial cell in the brain and regulate varied critical functions, including synaptic transmission and
plasticity. Research in the Reissner lab has revealed that astrocytes in the nucleus accumbens are significantly
structurally impaired following cocaine self-administration and extinction. In addition, preliminary data from our
lab indicate that rat long-access (LgA, 6h/day) self-administration followed by prolonged abstinence (45d)
leads to a significant ~40% decrease in astrocyte volume, surface area, and synaptic colocalization. However,
the mechanisms driving these observations are unknown. I hypothesize that downregulation of astrocyte
cytoskeletal dynamics is a major contributor to these effects. Accordingly, this proposal will examine how
astrocyte cytoskeletal dynamics are altered following chronic cocaine self-administration and prolonged
abstinence, and how manipulation of cytoskeletal proteins can influence cocaine seeking. Of note,
phosphorylation of ezrin, an actin-cytoskeleton linker protein that is abundantly and preferentially expressed in
astrocytes, is downregulated by acute cocaine exposure. Thus, the overarching hypothesis of this proposal is
that cocaine and abstinence-induced astrocyte structural deficits result from alterations in astrocyte
cytoskeletal dynamics, which further contribute to cocaine-seeking behaviors that are exacerbated following
long-term abstinence. To test this hypothesis, in Aim 1 I will measure the effects of cocaine self-administration
and abstinence on cytoskeletal proteins, including ezrin, and I will use an astrocyte-specific AAV to manipulate
ezrin expression, to examine its role astrocyte structure and further in cocaine-seeking behaviors. In Aim 2, I
will use a RiboTag AAV, to isolate astrocyte-specific mRNAs in conjunction with RNAseq as an unbiased
approach to measure cocaine and abstinence-induced changes in the astrocyte transcriptome that may
contribute to cocaine-seeking behavior. I will specifically analyze results to measure relative expression profiles
of cytoskeletal proteins among these astrocyte mRNAs. These results will provide a greater understanding of
how dysfunctions in astrocyte structure actively contribute to cocaine abuse and relapse.

## Key facts

- **NIH application ID:** 10607513
- **Project number:** 1F31DA057113-01A1
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Janay Franklin
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $38,617
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10607513

## Citation

> US National Institutes of Health, RePORTER application 10607513, Investigating cytoskeletal dynamics in astrocyte structure and cocaine seeking behavior (1F31DA057113-01A1). Retrieved via AI Analytics 2026-09-04 from https://api.ai-analytics.org/grant/nih/10607513. Licensed CC0.

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