{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:28:52Z","timestamp":1777858132683,"version":"3.51.4"},"reference-count":48,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T00:00:00Z","timestamp":1548288000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Samidorphan is a novel \u03bc-opioid antagonist with low intrinsic activity at \u03ba- and \u03b4-opioid receptors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>Because samidorphan is central nervous system-active, we investigated whether samidorphan (13.6, 40.8, 68 \u03bcg\/kg\/injection) served as a positive reinforcer in rats trained to self-administer heroin on a fixed ratio-5 schedule. Samidorphan\u2019s relative reinforcing effect was evaluated by progressive ratio\/break-point determination. Naltrexone (13.6, 40.8, 68 \u03bcg\/kg\/injection) and heroin (7.5, 15, 25 \u03bcg\/kg\/injection) were comparators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>All heroin doses maintained self-administration on fixed ratio-5 and progressive ratio\/break-points at levels significantly greater than saline. Samidorphan and naltrexone had similar profiles on fixed ratio-5 with one samidorphan dose serving as a positive reinforcer and one naltrexone dose showing a strong trend ( p=0.053) for positive reinforcement. The numbers of injections of every samidorphan and naltrexone dose were significantly lower than all heroin doses. The numbers of self-administered samidorphan and naltrexone injections\/session on fixed ratio-5 were not significantly different from one another. The mean inter-injection intervals for heroin were significantly shorter than for saline, whereas those of samidorphan and naltrexone were not. Progressive ratio break-points for samidorphan and naltrexone were not different from saline except for the highest dose of samidorphan. In addition, the progressive ratio break-points for samidorphan were not significantly different from those of naltrexone and were significantly lower than heroin. The samidorphan unit-doses evaluated in self-administration yielded plasma concentrations ranging between 25\u2013109% and 10\u201345% of the maximum concentration values in humans.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Overall, the profiles of samidorphan and naltrexone, which has no abuse liability, were similar in this model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0269881118822111","type":"journal-article","created":{"date-parts":[[2019,1,24]],"date-time":"2019-01-24T09:39:06Z","timestamp":1548322746000},"page":"383-391","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["Investigation of the reinforcing potential of samidorphan and naltrexone by fixed and progressive ratio intravenous self-administration testing in heroin-maintained rats"],"prefix":"10.1177","volume":"33","author":[{"given":"Sharon L","family":"Smith","sequence":"first","affiliation":[{"name":"RenaSci Ltd, BioCity, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Reginald L","family":"Dean","sequence":"additional","affiliation":[{"name":"Alkermes, Inc., Waltham, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark S","family":"Todtenkopf","sequence":"additional","affiliation":[{"name":"Alkermes, Inc., Waltham, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6128-9632","authenticated-orcid":false,"given":"David J","family":"Heal","sequence":"additional","affiliation":[{"name":"RenaSci Ltd, BioCity, Nottingham, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2019,1,24]]},"reference":[{"key":"bibr1-0269881118822111","doi-asserted-by":"publisher","DOI":"10.3109\/10826087609056165"},{"key":"bibr2-0269881118822111","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.118.249839"},{"key":"bibr3-0269881118822111","first-page":"181P","volume":"45","author":"Blakesley BC","year":"1972","journal-title":"Br J Pharmacol"},{"key":"bibr4-0269881118822111","first-page":"361","volume-title":"Behavioral Pharmacology: The Current Status","author":"Brady JV","year":"1985"},{"key":"bibr5-0269881118822111","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0704825"},{"key":"bibr6-0269881118822111","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.09m05080ecr"},{"key":"bibr7-0269881118822111","doi-asserted-by":"publisher","DOI":"10.1901\/jeab.1994.61-213"},{"key":"bibr8-0269881118822111","unstructured":"Center for Drug Evaluation and Research\/U.S. Food & Drug Administration, U.S. Department of Health and Human Services, Food and Drug Administration, Centre for Drug Evaluation and Research (2017). 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