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Therefore, most D<jats:sub>3<\/jats:sub>\u2010based medication development has focused on D<jats:sub>3<\/jats:sub> antagonists. However, D<jats:sub>3<\/jats:sub> antagonists do not attenuate cocaine intake under \u201ceasy\u201d self\u2010administration conditions, when response requirements are low. We evaluated a novel, highly selective and metabolically stable D<jats:sub>3<\/jats:sub> partial agonist, (\u00b1)VK4\u201040, for its efficacy in reducing cocaine intake and relapse to drug seeking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The impact of (\u00b1)VK4\u201040 on cocaine intake and relapse was evaluated using intravenous self\u2010administration procedures under a fixed\u2010ratio 2 reinforcement schedule and cocaine\u2010primed reinstatement conditions in rats. Optogenetic brain\u2010stimulation reward procedures were used to evaluate the interaction of (\u00b1)VK4\u201040 and cocaine in the mesolimbic dopamine system in mice. Sucrose self\u2010administration in rats and a conditioned place preference paradigm in mice were used to evaluate the abuse potential of (\u00b1)VK4\u201040 alone and other unwanted effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>(\u00b1)VK4\u201040 dose\u2010dependently reduced cocaine self\u2010administration and cocaine\u2010primed reinstatement of drug\u2010seeking behaviour. (\u00b1)VK4\u201040 also inhibited cocaine\u2010enhanced brain\u2010stimulation reward caused by optogenetic stimulation of dopamine neurons in the ventral tegmental area. (\u00b1)VK4\u201040 alone decreased brain\u2010stimulation reward but produced neither conditioned place preference nor place aversion. This new D<jats:sub>3<\/jats:sub> partial agonist also failed to alter oral sucrose self\u2010administration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>The novel D<jats:sub>3<\/jats:sub> partial agonist, (\u00b1)VK4\u201040 attenuates cocaine reward and relapse in rodents, without significant unwanted effects. These findings support further investigation of D<jats:sub>3<\/jats:sub> partial agonists as putative treatments for cocaine use disorder.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.15244","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T16:29:53Z","timestamp":1599064193000},"page":"4796-4807","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["(\u00b1)VK4\u201040, a novel dopamine D<sub>3<\/sub> receptor partial agonist, attenuates cocaine reward and relapse in rodents"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1843-227X","authenticated-orcid":false,"given":"Chloe J.","family":"Jordan","sequence":"first","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, Intramural Research Program  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"He","sequence":"additional","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, Intramural Research Program  Baltimore MD USA"},{"name":"Department of Neuroscience University of Pittsburgh  Pittsburgh PA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo\u2010Hua","family":"Bi","sequence":"additional","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, Intramural Research Program  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi\u2010Bing","family":"You","sequence":"additional","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, Intramural Research Program  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjing","family":"Cao","sequence":"additional","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, Intramural Research Program  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6482-8104","authenticated-orcid":false,"given":"Zheng\u2010Xiong","family":"Xi","sequence":"additional","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, Intramural Research Program  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy Hauck","family":"Newman","sequence":"additional","affiliation":[{"name":"Molecular Targets and Medications Discovery Branch National Institute on Drug Abuse, Intramural Research Program  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1581-9"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.224121"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21820"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200201210-00039"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300169"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2010.04.001"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14153"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300276"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-004-1807-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2005.05.011"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3254-y"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2018.03.020"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1527-3458.2003.tb00246.x"},{"key":"e_1_2_11_17_1","unstructured":"Gregory A.(2019).Global cocaine production reaches all\u2010time high after soaring 25% in one year UN Study Concludes.The Guardian[Online] Available fromhttps:\/\/www.independent.co.uk\/news\/world\/americas\/cocaine-production-record-levels-colombia-unodc-global-drugs-un-report-a8981616.html. 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