{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:09:13Z","timestamp":1790672953553,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2021,2,8]],"date-time":"2021-02-08T00:00:00Z","timestamp":1612742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Gambling and substance use disorders are highly comorbid. Both clinical populations are impulsive and exhibit risky decision\u2010making. Drug\u2010associated cues have long been known to facilitate habitual drug\u2010seeking, and the salient audiovisual cues embedded within modern gambling products may likewise encourage problem gambling. The dopamine neurons of the ventral tegmental area (VTA) are exquisitely sensitive to drugs of abuse, uncertain rewards, and reward\u2010paired cues and may therefore be the common neural substrate mediating synergistic features of both disorders. To test this hypothesis, we first gained specific inhibitory control over VTA dopamine neurons by transducing a floxed inhibitory DREADD (AAV5\u2010hSyn\u2010DIO\u2010hM4D(Gi)\u2010mCherry) in rats expressing Cre recombinase in tyrosine hydroxylase neurons. We then trained rats in our cued rat gambling task (crGT), inhibiting dopamine neurons throughout task acquisition and performance, before allowing them to self\u2010administer cocaine in the same diurnal period as crGT sessions. The trajectories of addiction differ in women and men, and the dopamine system may differ functionally across the sexes; therefore, we used male and female rats here. We found that inhibition of VTA dopamine neurons decreased cue\u2010induced risky choice and reduced motor impulsivity in males, but surprisingly, enhanced risky decision making in females. Inhibiting VTA dopamine neurons also prevented cocaine\u2010induced changes in decision making in both sexes, but nevertheless drove all animals to consume more cocaine. These findings show that chronic dampening of dopamine signalling can have both protective and deleterious effects on addiction\u2010relevant behaviours, depending on biological sex and dependent variable of interest.<\/jats:p>","DOI":"10.1111\/adb.13022","type":"journal-article","created":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T05:02:10Z","timestamp":1612933330000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Dopamine neurons gate the intersection of cocaine use, decision making, and impulsivity"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9400-2458","authenticated-orcid":false,"given":"Tristan J.","family":"Hynes","sequence":"first","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M.","family":"Hrelja","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1905-2199","authenticated-orcid":false,"given":"Brett A.","family":"Hathaway","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5803-4455","authenticated-orcid":false,"given":"Celine D.","family":"Hounjet","sequence":"additional","affiliation":[{"name":"UBC School of Medicine University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2131-0740","authenticated-orcid":false,"given":"Chloe S.","family":"Chernoff","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie A.","family":"Ebsary","sequence":"additional","affiliation":[{"name":"Department of Electrical and Computer Engineering University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8048-9111","authenticated-orcid":false,"given":"Graeme D.","family":"Betts","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4772-5821","authenticated-orcid":false,"given":"Brittney","family":"Russell","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukhbir","family":"Kaur","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-4471","authenticated-orcid":false,"given":"Catharine A.","family":"Winstanley","sequence":"additional","affiliation":[{"name":"Department of Psychology, Djavad Mowafaghian Centre for Brain Health University of British Columbia  Vancouver BC Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1364-6613(02)01960-5"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1037\/0894-4105.18.1.152"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.11.003"},{"key":"e_1_2_8_5_1","volume-title":"Addiction by Design: Machine Gambling in Las Vegas","author":"Sch\u00fcll ND","year":"2014"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0173(93)90013-P"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1171-18.2018"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.15010"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2225-15.2016"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3477-17.2018"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(92)90297-M"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/cn5002705"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2014.58"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3694"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1154-7"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-019-5173-z"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2017.161"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1037\/bne0000372"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2007.07.003"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1183-2"},{"key":"e_1_2_8_21_1","first-page":"98","article-title":"Chemogenetic inhibition of cells in the paramedian midbrain tegmentum increases locomotor activity in rats","volume":"2016","author":"Wirtshafter D","year":"1632","journal-title":"Brain Res"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13103"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.62"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12388"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0095392"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2016.235"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.140045"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.3109\/10401239509149623"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-019-05308-x"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.44"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1137073"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.05.024"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.96"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01114-5"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(94)90510-X"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2013.09.009"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13877"},{"issue":"7","key":"e_1_2_8_38_1","first-page":"1","article-title":"Prefrontal dopamine and behavioral flexibility: shifting from an \u201cinverted\u2010U\u201d toward a family of functions","volume":"62","author":"Floresco SB","year":"2013","journal-title":"Front Neurosci"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.03.028"},{"issue":"2","key":"e_1_2_8_40_1","first-page":"132","article-title":"Reward deficiency syndrome","volume":"84","author":"Blum K","year":"1996","journal-title":"Am Sci"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.114.1.3"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.07.015"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.20229"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0030-17.2017"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300301"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(87)90451-4"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.18-13-05068.1998"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.890140302"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.64.11.1575"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.04.044"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.4013"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13022","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/adb.13022","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T12:08:51Z","timestamp":1693138131000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.13022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,8]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/adb.13022"],"URL":"https:\/\/doi.org\/10.1111\/adb.13022","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.06.29.179069","asserted-by":"object"}]},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,8]]},"assertion":[{"value":"2020-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-01-21","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13022"}}