{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T05:16:06Z","timestamp":1766639766571,"version":"3.48.0"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:00:00Z","timestamp":1766448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R00 DA047426"],"award-info":[{"award-number":["R00 DA047426"]}]},{"name":"NIH","award":["R01 HL179583"],"award-info":[{"award-number":["R01 HL179583"]}]},{"name":"NIH","award":["R24 OD038116"],"award-info":[{"award-number":["R24 OD038116"]}]},{"name":"NIH","award":["R41NS139906"],"award-info":[{"award-number":["R41NS139906"]}]},{"name":"Behavior Research Foundation","award":["31580"],"award-info":[{"award-number":["31580"]}]},{"name":"Department of Pediatrics, Children\u2019s Research Institute, Medical College of Wisconsin, Milwaukee, WI"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The United States is currently facing a drug overdose epidemic. The nucleus accumbens core (NAcore), a brain region critical for reward and aversion behaviors, undergoes structural and functional synaptic adaptations in response to chronic drug exposure. However, the molecular mechanisms underlying these adaptations remain poorly understood. In this study, we investigate the role of dual-specificity phosphatase 5 (DUSP5), a phosphatase known to deactivate extracellular signal-regulated kinase (ERK), in cocaine-induced neuroplasticity. While prior research has linked other DUSP family members to various drugs of abuse, the specific role of DUSP5 in cocaine addiction remains unexplored. We hypothesized that lack of DUSP5 contributes to cocaine-induced maladaptive synaptic plasticity in NAcore. To test this, we employed a rat cocaine self-administration model and molecular analyses and mined publicly available single-cell RNA sequencing data from cocaine-treated NAcore. Our findings reveal a role for DUSP5 in cocaine-related synaptic and behavioral adaptations, highlighting DUSP5 and DUSP5-associated signaling pathways as potential mechanisms underlying substance use disorders and as candidates for therapeutic intervention.<\/jats:p>","DOI":"10.3390\/cells15010032","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T11:22:14Z","timestamp":1766575334000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DUSP5 Downregulation in Nucleus Accumbens Core Correlates with Cocaine-Induced Maladaptive Synaptic Plasticity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6448-2633","authenticated-orcid":false,"given":"Juan Pablo","family":"Taborda-Bejarano","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Meyerink","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7792-3450","authenticated-orcid":false,"given":"Debbie C.","family":"Crans","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 90523, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3555-6119","authenticated-orcid":false,"given":"Ramani","family":"Ramchandran","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Neonatology, Children\u2019s Research Institute (CRI) Developmental Vascular Biology Program, Translational and Biomedical Research Center, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3141-9571","authenticated-orcid":false,"given":"Constanza","family":"Garcia-Keller","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.1111\/add.16318","article-title":"Charting the fourth wave: Geographic, temporal, race\/ethnicity and demographic trends in polysubstance fentanyl overdose deaths in the United States, 2010\u20132021","volume":"118","author":"Friedman","year":"2023","journal-title":"Addiction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1097\/YCO.0000000000000717","article-title":"The rise of illicit fentanyls, stimulants and the fourth wave of the opioid overdose crisis","volume":"34","author":"Ciccarone","year":"2021","journal-title":"Curr. 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