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In addition, dysfunction of the glutamate transporter 1 (GLT\u20101) in the nucleus accumbens (NAc) has also been proposed as a mechanism underlying drug addiction. However, the cellular and synaptic impact of GLT\u20101 alterations in the NAc remain unclear. Here we show in the NAc that 10\u2009days withdraw after 5\u2009days treatment with cocaine or amphetamine decreases GLT\u20101 expression in astrocytes, which results in the prolongation of the excitatory postsynaptic potential (EPSP) decay kinetics in D1 receptor\u2010containing medium spiny neurons (D1R\u2010MSNs). 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\u2010treated mice. In contrast to D1\u2010MSNs, D2\u2010MSNs did not display changes in EPSP kinetics and synaptic plasticity. Notably, the psychostimulant\u2010induced synaptic transmission and synaptic plasticity effects were absent in IP3R2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, which lack astrocyte calcium signal, but were mimicked by the selective astrocytes stimulation with DREADDs. Finally, ceftriaxone, which upregulates GLT\u20101, restored normal GLT\u20101 function, EPSP kinetics, and synaptic plasticity in psychostimulant\u2010treated mice. Therefore, we propose that cocaine and amphetamine increase dopaminergic levels in the NAc, which stimulates astrocytes and downregulates the GLT\u20101. The decreased GLT\u20101 function prolonged the EPSP kinetics, leading to the modulation of the STDP, transforming the LTP observed in control animals into LTD in psychostimulant\u2010treated mice. Present work reveals a novel mechanism underlying the synaptic plasticity changes induced by these drugs of abuse.\n                  <\/jats:p>","DOI":"10.1002\/glia.24672","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T03:40:22Z","timestamp":1736739622000},"page":"1051-1067","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Astrocytes Mediate Psychostimulant\u2010Induced Alterations of\u00a0Spike\u2010Timing Dependent Synaptic Plasticity"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4113-6150","authenticated-orcid":false,"given":"Samuel","family":"Alberquilla","sequence":"first","affiliation":[{"name":"Cajal Institute, CSIC  Madrid Spain"},{"name":"CIBERNED, Instituto de Salud Carlos III  Madrid 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