# Astrocyte-mediated mechanisms of cocaine seeking

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $336,415

## Abstract

Project Summary/Abstract
Propensity toward relapse is a hallmark feature of addiction. Hence, understanding the cellular mechanisms
responsible for relapse vulnerability represents an important focus of addiction research. One significant and
long-lasting cellular adaptation observed in response to multiple drugs of abuse is downregulation of astroglial
glutamate transporter GLT-1. However, relatively very little is known about how drug self-administration affects
astrocytes beyond GLT-1 expression, or how astrocytes may contribute to mechanisms of drug seeking.
Results collected during the preceding K99/R00 award indicate that restored expression of GLT-1 is pivotal to
the mechanism of action of multiple compounds that reduce behavioral measures of relapse in the rat self-
administration and reinstatement model of addiction. Preliminary data also indicate that downregulation of
GLT-1 by cocaine is accompanied by reduced expression of glial fibrillary acidic protein (GFAP) and a
retraction of astrocytes in the nucleus accumbens core. Astrocyte retraction is characterized by decreased
surface area, volume, and decreased synaptic contacts. This finding represents a heretofore-unappreciated
fundamental consequence of cocaine use on astrocyte cell biology. Thus, decreased GLT-1 expression is a
component of larger-scale adaptions in astrocyte biology that occur following chronic cocaine use. These
findings have led to the hypothesis that astrocyte retraction in the nucleus accumbens of cocaine-withdrawn
rats contributes to synaptic adaptations that drive cocaine seeking. In order to test this hypothesis, the specific
goals of this proposal are: (1) to determine when during the addiction cycle the morphological effects on
astrocytes are induced (2) to determine the functional relationship between astrocyte retraction and synaptic
adaptations believed to underlie cocaine seeking, and (3) to determine the relationship between astrocyte
retraction and drug seeking after cessation of drug use. These questions will be addressed by combining rat
cocaine self-administration with behavioral measures of cocaine seeking, high-resolution imaging of
fluorescently labeled astrocytes, and whole cell patch-clamp electrophysiology. These studies will provide
novel insight into how cocaine-dependent adaptations in astrocyte dynamics contribute to the cellular and
behavioral pathologies characteristic of psychostimulant addiction. These studies will also provide important
information toward the translational potential of astrocytes as a pharmacotherapeutic target for substance use
disorders.

## Key facts

- **NIH application ID:** 9902393
- **Project number:** 5R01DA041455-05
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Kathryn Joanna Reissner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,415
- **Award type:** 5
- **Project period:** 2016-06-15 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902393

## Citation

> US National Institutes of Health, RePORTER application 9902393, Astrocyte-mediated mechanisms of cocaine seeking (5R01DA041455-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9902393. Licensed CC0.

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