{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T02:49:04Z","timestamp":1788922144476,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA048134"],"award-info":[{"award-number":["DA048134"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["MH125996"],"award-info":[{"award-number":["MH125996"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001391","name":"Whitehall Foundation","doi-asserted-by":"publisher","award":["2020\u201012\u201035"],"award-info":[{"award-number":["2020\u201012\u201035"]}],"id":[{"id":"10.13039\/100001391","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000882","name":"Brain Research Foundation","doi-asserted-by":"publisher","award":["BRFSG\u20102022\u201006"],"award-info":[{"award-number":["BRFSG\u20102022\u201006"]}],"id":[{"id":"10.13039\/100000882","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS121780"],"award-info":[{"award-number":["NS121780"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","award":["28113"],"award-info":[{"award-number":["28113"]}],"id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Identifying shared neural mechanisms influenced by diverse classes of drugs of abuse is essential for understanding addiction and for developing broad\u2010spectrum treatments for substance use disorders. Previous studies indicate that many drugs of abuse increase dopamine output from the ventral tegmental area (VTA) by altering the balance of excitatory and inhibitory inputs onto dopamine neurons, thereby promoting maladaptive plasticity within reward circuits. Here, we demonstrate in rats that acute injections of morphine and cocaine, but not saline, disrupt chloride homeostasis in VTA GABA neurons. This disruption is characterised by a depolarised GABA\n                    <jats:sub>A<\/jats:sub>\n                    reversal potential, impaired chloride extrusion, and posttranslational downregulation of the potassium chloride cotransporter KCC2. Although previous studies linked drug\u2010induced posttranslational downregulation of KCC2 in the VTA to glucocorticoid receptor activation, we found that a glucocorticoid receptor antagonist did not prevent cocaine\u2010 and morphine\u2010induced disruption of chloride homeostasis. Instead, our data show that dopamine D1\/D5 receptor activation is both necessary and sufficient for these alterations. Notably, chloride homeostasis remains impaired for several weeks after volitional morphine self\u2010administration, indicating long\u2010lasting plasticity. These findings complement previous work on nicotine and alcohol, suggesting a shared mechanism of inhibitory plasticity in the VTA following drug exposure. Given that chloride dysregulation in VTA GABA neurons influences downstream circuit function and promotes maladaptive behaviours associated with drug use, we propose KCC2 as a promising therapeutic target for substance use disorders.\n                  <\/jats:p>","DOI":"10.1111\/adb.70104","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T05:40:31Z","timestamp":1764913231000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cocaine and Morphine Converge to Disrupt Chloride Homeostasis in Ventral Tegmental Area GABA Neurons"],"prefix":"10.1111","volume":"30","author":[{"given":"Anna\u00a0C.","family":"Pearson","sequence":"first","affiliation":[{"name":"Department of Pharmacology &amp; Physiology Georgetown University  Washington DC USA"},{"name":"Interdisciplinary Program in Neuroscience Georgetown University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blake\u00a0A.","family":"Kimmey","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison\u00a0B.","family":"Taormina","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0498-0005","authenticated-orcid":false,"given":"William\u00a0M.","family":"Holden","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Mahoney Institute for Neurosciences, Perelman School for Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0362-3708","authenticated-orcid":false,"given":"Alexey","family":"Ostroumov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology &amp; Physiology Georgetown University  Washington DC USA"},{"name":"Interdisciplinary Program in Neuroscience Georgetown University  Washington DC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1578"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ps.40.020189.001203"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.165"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.23603"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.100085"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.09.029"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2018.03.030"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0348\u201019.2020"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.221"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014\u20104886(03)00213\u20109"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23\u201023\u201008237.2003"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035\u2010022\u201003126\u20105"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.059"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.06.024"},{"key":"e_1_2_10_16_1","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos G.","year":"2007"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2018.01.008"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010019\u201005450\u20106"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21\u201005\u201001452.2001"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1385\/MN:29:3:243"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.117069"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2274"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/429815"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4036\u201014.2015"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213\u2010013\u20103002\u20103"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2013.06.006"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1054\/npep.1999.0007"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0165\u20105728(01)00299\u20105"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20103057(93)90106\u20104"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(87)90953\u2010X"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749\u20106632.1986.tb23629.x"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010psych\u2010010418\u2010103337"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5179\u201005.2006"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1001\u201008.2008"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.05.024"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.09.051"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471\u20104159.2004.02392.x"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23\u201008\u201003531.2003"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.2003.01824.x"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050365"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1182"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2806"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3257\u201006.2006"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.32"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.11.005"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010023\u201001547\u20106"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2021.08.052"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010022\u201001126\u20101"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112069"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0091\u20103057(97)00043\u20109"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abm5217"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593\u2010021\u201000898\u20102"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201023906\u20102"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11657"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.70104","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.70104","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.70104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T19:10:28Z","timestamp":1770923428000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.70104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":53,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/adb.70104"],"URL":"https:\/\/doi.org\/10.1111\/adb.70104","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"2025-07-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70104"}}