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Accumulating literature demonstrates that cocaine self\u2010administration in rodent models induces structural changes within astrocytes that may influence their interaction with the surrounding neurons. Here, we provide evidence that cocaine impacts astrocytes at the functional level and alters neuronal sensitivity to astrocyte\u2010derived glutamate. We report that a 14\u2010day period of short access to cocaine (2\u2009h\/day) decreases spontaneous astrocytic Ca<jats:sup>2+<\/jats:sup> transients and precipitates changes in astrocyte network activity in the nucleus accumbens shell. This is accompanied by increased prevalence of slow inward currents, a physiological marker of neuronal activation by astrocytic glutamate, in a subset of medium spiny neurons. Within, but not outside, of this subset, we observe an increase in duration and frequency of N\u2010methyl\u2010D\u2010aspartate (NMDA) receptor\u2010mediated synaptic events. Additionally, we find that the link between synaptic NMDA receptor plasticity and neuron sensitivity to astrocytic glutamate is maintained independent of drug exposure and is observed in both cocaine and saline control animals. Imaging analyses of neuronal Ca<jats:sup>2+<\/jats:sup> activity show no effect of cocaine self\u2010administration on individual cells or on neuronal network activity in brain slices. Therefore, our data indicate that cocaine self\u2010administration promotes astrocyte\u2010specific functional changes that can be linked to increased glutamate\u2010mediated coupling with principal neurons in the nucleus accumbens. Such coupling may be spatially restricted as it does not result in a broad impact on network structure of local neuronal circuits.<\/jats:p>","DOI":"10.1111\/adb.13042","type":"journal-article","created":{"date-parts":[[2021,4,17]],"date-time":"2021-04-17T05:28:18Z","timestamp":1618637298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cocaine experience induces functional adaptations in astrocytes: Implications for synaptic plasticity in the nucleus accumbens shell"],"prefix":"10.1111","volume":"26","author":[{"given":"Bernadette","family":"O'Donovan","sequence":"first","affiliation":[{"name":"Department of Neuroscience, College of Medicine University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Austin","family":"Neugornet","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, College of Medicine University of Kentucky  Lexington 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