Plasticity in astrocyte subpopulations regulates heroin relapse

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Abstract

Opioid use disorder (OUD) produces detrimental personal and societal consequences. Astrocytes are a major cell group in the brain that receives little attention in mediating OUD. We determined how astrocytes and the astroglial glutamate transporter, GLT-1, in the nucleus accumbens core adapt and contribute to heroin seeking in rats. Seeking heroin, but not sucrose, produced two transient forms of plasticity in different astroglial subpopulations. Increased morphological proximity to synapses occurred in one subpopulation and increased extrasynaptic GLT-1 expression in another. Augmented synapse proximity by astroglia occurred selectively at D2-dopamine receptor–expressing dendrites, while changes in GLT-1 were not neuron subtype specific. mRNA-targeted antisense inhibition of either morphological or GLT-1 plasticity promoted cue-induced heroin seeking. Thus, we show that heroin cues induce two distinct forms of transient plasticity in separate astroglial subpopulations that dampen heroin relapse.

Abstract

Different subpopulations of astrocytes engage with accumbens synapses to dampen heroin relapse.

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Most cited references 67

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Addiction is associated with neuroplasticity in the corticostriatal brain circuitry that is important for guiding adaptive behaviour. The hierarchy of corticostriatal information processing that normally permits the prefrontal cortex to regulate reinforcement-seeking behaviours is impaired by chronic drug use. A failure of the prefrontal cortex to control drug-seeking behaviours can be linked to an enduring imbalance between synaptic and non-synaptic glutamate, termed glutamate homeostasis. The imbalance in glutamate homeostasis engenders changes in neuroplasticity that impair communication between the prefrontal cortex and the nucleus accumbens. Some of these pathological changes are amenable to new glutamate- and neuroplasticity-based pharmacotherapies for treating addiction.

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Author and article information

Contributors

Anna Kruyer:

ORCID: https://orcid.org/0000-0001-9267-9492

Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: VisualizationRole: Writing - original draftRole: Writing - review & editing

Ariana Angelis:

ORCID: https://orcid.org/0000-0003-3432-5228

Role: Formal analysisRole: Investigation

Constanza Garcia-Keller: Role: InvestigationRole: Methodology

Hong Li:

ORCID: https://orcid.org/0000-0002-6065-5100

Role: Formal analysisRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing - review & editing

Peter W. Kalivas: Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: VisualizationRole: Writing - review & editing

Journal

Journal ID (nlm-ta): Sci Adv

Journal ID (iso-abbrev): Sci Adv

Journal ID (publisher-id): sciadv

Journal ID (hwp): advances

Title: Science Advances

Publisher: American Association for the Advancement of Science

ISSN (Electronic): 2375-2548

Publication date Collection: August 2022

Publication date (Electronic, pub): 10 August 2022

Volume: 8

Issue: 31

Electronic Location Identifier: eabo7044

Affiliations

[ ¹ ]Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA.

[ ² ]Department of Biostatistics & Bioinformatics, Medical University of South Carolina, Charleston, SC, USA.

Author notes

[* ]Corresponding author. Email: kruyer@ 123456musc.edu

Author information

Anna Kruyer https://orcid.org/0000-0001-9267-9492

Ariana Angelis https://orcid.org/0000-0003-3432-5228

Hong Li https://orcid.org/0000-0002-6065-5100

Article

Publisher ID: abo7044

DOI: 10.1126/sciadv.abo7044

PMC ID: 9365285

PubMed ID: 35947652

SO-VID: 10bef651-7c18-48a8-83b5-f030a6537fdc

Copyright © Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

History

Date received : 19 February 2022

Date accepted : 24 June 2022

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100000001, National Science Foundation;

Award ID: OIA 1539034

Funded by: FundRef http://dx.doi.org/10.13039/100000001, National Science Foundation;

Award ID: OIA 1539034