{"doi":"10.1002/glia.24672","title":"Astrocytes Mediate Psychostimulant‐Induced Alterations of Spike‐Timing Dependent Synaptic Plasticity","abstract":"ABSTRACT At cellular and circuit levels, drug addiction is considered a dysregulation of synaptic plasticity. In addition, dysfunction of the glutamate transporter 1 (GLT‐1) in the nucleus accumbens (NAc) has also been proposed as a mechanism underlying drug addiction. However, the cellular and synaptic impact of GLT‐1 alterations in the NAc remain unclear. Here we show in the NAc that 10 days withdraw after 5 days treatment with cocaine or amphetamine decreases GLT‐1 expression in astrocytes, which results in the prolongation of the excitatory postsynaptic potential (EPSP) decay kinetics in D1 receptor‐containing medium spiny neurons (D1R‐MSNs). Using the spike timing dependent plasticity (STDP) paradigm, we found that enlargement of EPSP duration results in switching the LTP elicited in control animals to LTD in psychostimulant‐treated mice. In contrast to D1‐MSNs, D2‐MSNs did not display changes in EPSP kinetics and synaptic plasticity. Notably, the psychostimulant‐induced synaptic transmission and synaptic plasticity effects were absent in IP3R2 −/− mice, which lack astrocyte calcium signal, but were mimicked by the selective astrocytes stimulation with DREADDs. Finally, ceftriaxone, which upregulates GLT‐1, restored normal GLT‐1 function, EPSP kinetics, and synaptic plasticity in psychostimulant‐treated mice. Therefore, we propose that cocaine and amphetamine increase dopaminergic levels in the NAc, which stimulates astrocytes and downregulates the GLT‐1. The decreased GLT‐1 function prolonged the EPSP kinetics, leading to the modulation of the STDP, transforming the LTP observed in control animals into LTD in psychostimulant‐treated mice. Present work reveals a novel mechanism underlying the synaptic plasticity changes induced by these drugs of abuse.","journal":"Glia","year":2025,"id":538472,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9455,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":632231,"name":"Carmen Nanclares","orcid":"0000-0003-4420-266X","position":1,"is_corresponding":false},{"id":1425058,"name":"Sara Expósito","orcid":"0000-0002-8527-0573","position":2,"is_corresponding":false},{"id":1425434,"name":"Grace Gall","orcid":null,"position":3,"is_corresponding":false},{"id":232009,"name":"Paulo Kofuji","orcid":"0000-0002-4840-9986","position":4,"is_corresponding":false},{"id":232010,"name":"Alfonso Araque","orcid":"0000-0003-3840-1144","position":5,"is_corresponding":false},{"id":232007,"name":"E. Martin","orcid":"0000-0003-1768-3488","position":6,"is_corresponding":false},{"id":1425059,"name":"Rosario Moratalla","orcid":"0000-0002-7623-8010","position":7,"is_corresponding":false},{"id":1425057,"name":"Samuel Alberquilla","orcid":"0000-0003-4113-6150","position":0,"is_corresponding":true}],"reference_count":85,"raw_metadata":null,"created_at":"2026-07-19T02:52:21.389196Z","pmid":"39801264","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}