{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:41:11Z","timestamp":1787888471129,"version":"build-2784847793"},"reference-count":63,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T00:00:00Z","timestamp":1595030400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["DA023957"],"award-info":[{"award-number":["DA023957"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The dopamine D3 receptor is a prime target for developing treatments for cocaine use disorders (CUDs). In this study, we conducted a pre-clinical investigation of the therapeutic potential of a long-acting, D3 receptor partial agonist, MC-25-41. Male rats were pre-treated with MC-25-41 (vehicle, 1.0, 3.0, 5.6, or 10 mg\/kg, intraperitoneal (IP)) five minutes prior to tests of cocaine or sucrose intake on either a progressive ratio schedule of reinforcement or a variable interval 60 s multiple schedule consisting of 4, 15-min components with sucrose or cocaine available in alternating components. A separate cohort of rats was tested on a within-session, dose-reduction procedure to determine the effects of MC-25-41 on demand for cocaine using a behavioral economics analysis. Finally, rats were tested for effects of MC-25-41 on spontaneous and cocaine-induced locomotion. MC-25-41 failed to alter locomotion, but reduced reinforcement rates for both cocaine and sucrose on the low-effort, multiple schedule. However, on the higher-effort, progressive ratio schedule of cocaine reinforcement, MC-25-41 reduced infusions, and active lever presses at doses that did not alter sucrose intake. The behavioral economics analysis showed that MC-25-41 also increased cocaine demand elasticity compared to vehicle, indicating a reduction in consumption as price increases. Together, these results suggest that similar to other D3-selective antagonists and partial agonists, MC-25-41 reduces motivation for cocaine under conditions of high cost but has the added advantage of a long half-life (&gt;10 h). These findings suggest that MC-25-41 may be a suitable pre-clinical lead compound for development of medications to treat CUDs.<\/jats:p>","DOI":"10.3390\/biom10071076","type":"journal-article","created":{"date-parts":[[2020,7,20]],"date-time":"2020-07-20T10:59:38Z","timestamp":1595242778000},"page":"1076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Long-Acting D3 Partial Agonist MC-25-41 Attenuates Motivation for Cocaine in Sprague-Dawley Rats"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6097-9092","authenticated-orcid":false,"given":"Gregory L.","family":"Powell","sequence":"first","affiliation":[{"name":"School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Namba","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7796-5597","authenticated-orcid":false,"given":"Annika","family":"Vannan","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-4460","authenticated-orcid":false,"given":"John Paul","family":"Bonadonna","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Carlson","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Mendoza","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Jen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Moulder Center for Drug Discovery Research, Temple University School of Pharmacy, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Luetdke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Neuroscience, Institute for Healthy Aging, University of North Texas Health Science Center, Fort Worth, TX 76107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin E.","family":"Blass","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Moulder Center for Drug Discovery Research, Temple University School of Pharmacy, Philadelphia, PA 19140, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2629-3708","authenticated-orcid":false,"given":"Janet L.","family":"Neisewander","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Arizona State University, PO Box 874501, Tempe, AZ 85287-4501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"430","DOI":"10.2105\/AJPH.2016.303627","article-title":"Recent increases in cocaine-related overdose deaths and the role of opioids","volume":"107","author":"Jones","year":"2017","journal-title":"Am. 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