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SUD is the uncontrolled and chronic use of substances despite the negative consequences resulting from this use. The progressive nature of addiction is organized into a testable framework, the neurobiological stage-based model, that includes three behavioral stages: (1) binge\/intoxication, (2) withdrawal\/negative affect, and (3) preoccupation\/anticipation. Human studies offer limited opportunities for mechanistic insights into these; therefore, model organisms, like Drosophila melanogaster, are necessary for understanding SUD. Drosophila is a powerful model organism that displays a variety of SUD-like behaviors consistent with human and mammalian substance use, making flies a great candidate to study mechanisms of behavior. Additionally, there are an abundance of genetic tools like the GAL4\/UAS and CRISPR\/Cas9 systems that can be used to gain insight into the molecular mechanisms underlying the endophenotypes of the three-stage model. This review uses the three-stage framework and discusses how easily testable endophenotypes have been examined with experiments using Drosophila, and it outlines their potential for investigating other endophenotypes.<\/jats:p>","DOI":"10.3390\/ijms241310909","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T16:06:37Z","timestamp":1688141197000},"page":"10909","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Stage-Based Model of Addiction\u2014Using Drosophila to Investigate Alcohol and Psychostimulant Responses"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5909-1312","authenticated-orcid":false,"given":"Pearl N.","family":"Cummins-Beebee","sequence":"first","affiliation":[{"name":"Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Neuroscience Graduate Program, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie M.","family":"Chvilicek","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Neuroscience Graduate Program, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3813-5723","authenticated-orcid":false,"given":"Adrian","family":"Rothenfluh","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Molecular Medicine Program, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Neuroscience Graduate Program, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Department of Neurobiology, University of Utah, Salt Lake City, UT 84112, USA"},{"name":"Department of Human Genetics, University of Utah, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1111\/add.14234","article-title":"Global statistics on alcohol, tobacco and illicit drug use: 2017 status report","volume":"113","author":"Peacock","year":"2018","journal-title":"Addiction"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e140","DOI":"10.1038\/tp.2012.54","article-title":"The genetics of addiction\u2014A translational perspective","volume":"2","author":"Agrawal","year":"2012","journal-title":"Transl. 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