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Published on: October 5, 2021
Astrocytic D1 Dopamine-Signaling Regulates Synaptic Remodeling and Cocaine Seeking
Biorxiv : the Preprint Server for Biology
|June 4, 2026
Summary
Astrocytes, not just neurons, use D1-type receptors (D1R) to shape drug memories. Targeting astrocytic D1R in the nucleus accumbens shell accelerates cocaine craving extinction and reduces relapse risk.
Area of Science:
- Neuroscience
- Molecular Biology
- Addiction Research
Background:
- Dopaminergic signaling via D1-type receptors (D1R) in the nucleus accumbens shell (NAcSh) is crucial for drug-related memory formation.
- D1R is present in both NAcSh neurons and astrocytes, but the role of astrocytic D1R in drug addiction plasticity is unclear.
Purpose of the Study:
- To investigate the specific role of astrocytic D1R in the NAcSh during cocaine seeking and relapse.
- To determine if astrocytic D1R influences synaptic plasticity and circuit remodeling associated with cocaine use.
Main Methods:
- Utilized mouse NAcSh slices to examine astrocytic Ca2+ activity in response to D1R agonists.
- Employed astrocyte-specific D1R knockdown prior to cocaine self-administration in mice.
- Assessed cocaine-induced silent synapse generation, NAcSh circuit remodeling, and behavioral outcomes (extinction, reinstatement).
Main Results:
- D1R agonists increased astrocytic Ca2+ activity in NAcSh slices, an effect reduced by astrocyte-specific D1R knockdown.
- Knockdown of astrocytic D1R in the NAcSh inhibited cocaine-induced silent synapse formation and subsequent circuit remodeling.
- Behaviorally, NAcSh astrocytic D1R knockdown expedited cocaine seeking extinction and diminished cue-induced reinstatement.
Conclusions:
- Astrocytic D1R is a key mediator of NAcSh dopamine signaling during cocaine experience.
- Targeting astrocytic D1R influences synaptic plasticity and neural network changes underlying drug seeking and relapse.
- Astrocytic D1R represents a potential therapeutic target for addiction treatment.
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