{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T05:41:14Z","timestamp":1792042874681,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T00:00:00Z","timestamp":1715472000000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R00DA050575"],"award-info":[{"award-number":["R00DA050575"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Synthetic opioids such as fentanyl contribute to the vast majority of opioid\u2010related overdose deaths, but fentanyl use remains broadly understudied. Like other substances with misuse potential, opioids cause lasting molecular adaptations to brain reward circuits, including neurons in the ventral tegmental area (VTA). The VTA contains numerous cell types that play diverse roles in opioid use and relapse; however, it is unknown how fentanyl experience alters the transcriptional landscape in specific subtypes. Here, we performed single nuclei RNA sequencing to study transcriptional programs in fentanyl\u2010experienced mice. Male and female C57\/BL6 mice self\u2010administered intravenous fentanyl (1.5\u00a0\u03bcg\/kg\/infusion) or saline for 10\u00a0days. After 24\u2009h abstinence, VTA nuclei were isolated and prepared for sequencing on the 10\u00d7 platform. We identified different patterns of gene expression across cell types. In dopamine neurons, we found enrichment of genes involved in growth hormone signalling. In dopamine\u2010glutamate\u2010GABA combinatorial neurons, and some GABA neurons, we found enrichment of genes involved in Pi3k\u2010Akt signalling. In glutamate neurons, we found enrichment of genes involved in cholinergic signalling. We identified transcriptional regulators for the differentially expressed genes in each neuron cluster, including downregulated transcriptional repressor Bcl6, and upregulated transcription factor Tcf4. We also compared the fentanyl\u2010induced gene expression changes identified in mouse VTA with a published rat dataset in bulk VTA, and found overlap in genes related to GABAergic signalling and extracellular matrix interaction. Together, we provide a comprehensive picture of how fentanyl self\u2010administration alters the transcriptional landscape of the mouse VTA that serves as the foundation for future mechanistic studies.<\/jats:p>","DOI":"10.1111\/adb.13403","type":"journal-article","created":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:45:03Z","timestamp":1715553903000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Transcriptional signatures of fentanyl use in the mouse ventral tegmental area"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3177-831X","authenticated-orcid":false,"given":"Megan E.","family":"Fox","sequence":"first","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"},{"name":"Department of Pharmacology The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annalisa","family":"Montemarano","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandria E.","family":"Ostman","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahashweta","family":"Basu","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Herb","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth A.","family":"Ament","sequence":"additional","affiliation":[{"name":"Institute for Genome Sciences University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Logan D.","family":"Fox","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Perioperative Medicine The Pennsylvania State University College of Medicine  Hershey Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,12]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"crossref","unstructured":"SpencerMR Mini\u00f1oAM WarnerM.Drug overdose deaths in the United States 2001\u20102021. NCHS Data Brief.2022;(457).","DOI":"10.15620\/cdc:122556"},{"key":"e_1_2_7_3_1","unstructured":"Drug Enforcement Administration.Counterfeit prescription pills containing fentanyls: a global threat;2016. Accessed April 13 2022.https:\/\/www.safemedicines.org\/2018\/06\/fentanyl-has-created-a-new-kind-of-21st-century-drug-kingpin.html"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386\u2010018\u20100234\u20102"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/CSHPERSPECT.A039362"},{"issue":"1","key":"e_1_2_7_6_1","first-page":"489","article-title":"Neuroanatomical sites mediating the motivational effects of opioids as mapped by the conditioned place preference paradigm in rats","volume":"264","author":"Bals\u2010Kubik R","year":"1993","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091\u20103057(80)80039\u20106"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024\u20103205(81)90148\u2010X"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.135"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5032\u201005.2006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1222265"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.10.012"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3939"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0062\u201005.2005"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3932"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.JCHEMNEU.2015.12.016"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.165"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.CELREP.2022.110616"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2019.00078"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNCIR.2022.867053\/PDF"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/NPP.2016.32"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.02.012"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/S00429\u2010012\u20100452\u2010Z\/TABLES\/2"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3823"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpsgos.2021.07.011"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.08.080"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROPHARM.2022.108986"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BIOPSYCH.2022.08.023"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.BPSGOS.2021.04.009"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010020\u201005657\u2010y"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/S13059\u2010019\u20101874\u20101"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009234\u20106"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201025960\u20102"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1003731"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2020.03.003"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460\u20109568.1998.00368.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/IJNP\/PYAD013"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386\u2010023\u201001634\u2010z"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041\u2010019\u20100435\u20106"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1812"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/FNINT.2022.899637\/BIBTEX"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104519.1999.0731520.x"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12925"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386\u2010021\u201001032\u20103"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41380\u2010023\u201002290\u2010X"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/J.1369\u20101600.2010.00281.X"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/S41386\u2010023\u201001637\u2010W"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEUROSCIENCE.2012.03.056"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.3390\/IJMS23158106"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19\u201006\u201002347.1999"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/J.NEURON.2014.04.030"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13403","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T10:32:23Z","timestamp":1732876343000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.13403"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/adb.13403"],"URL":"https:\/\/doi.org\/10.1111\/adb.13403","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.12.18.572172","asserted-by":"object"}]},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2024-01-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13403"}}