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Using an extended-access self-administration model and in vivo\n                    <jats:sup>1<\/jats:sup>\n                    H-magnetic resonance spectroscopy, we found that lactate synthesis in the central amygdala (CeA) is required for the intensified cocaine craving after prolonged withdrawal. Furthermore, incubated cocaine seeking was associated with a selective increase in monocarboxylate transporter 2 (MCT2) and MCT4 expression levels. Down-regulation of astrocytic MCT4 or neuronal MCT2 using targeted antisense oligonucleotides or cell type\u2013specific shRNA attenuated cocaine craving and reduced the expression of plasticity-related proteins and excitatory synaptic transmission. Meanwhile, lactate administration rescued MCT4 but not MCT2 disruption\u2013induced behavioral changes due to the inability of lactate to be transported into neurons. Together, our study highlights the critical role of astrocyte-neuron lactate transport in the CeA in the incubation of cocaine craving and suggests a potential therapeutic target for drug addiction.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adi4462","type":"journal-article","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T13:59:21Z","timestamp":1698242361000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":19,"title":["Disrupting astrocyte-neuron lactate transport prevents cocaine seeking after prolonged withdrawal"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7780-8476","authenticated-orcid":true,"given":"Wenjun","family":"Chen","sequence":"first","affiliation":[{"name":"National Institute on Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China."},{"name":"School of Basic Medical Sciences, Peking 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