{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:15:15Z","timestamp":1785863715701,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T00:00:00Z","timestamp":1648684800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 1200287"],"award-info":[{"award-number":["FONDECYT 1200287"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["FONDECYT 3210276"],"award-info":[{"award-number":["FONDECYT 3210276"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002848","name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo","doi-asserted-by":"publisher","award":["ACT210012"],"award-info":[{"award-number":["ACT210012"]}],"id":[{"id":"10.13039\/501100002848","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>An animal model of voluntary oral morphine consumption would allow for a pre-clinical evaluation of new treatments aimed at reducing opioid intake in humans. However, the main limitation of oral morphine consumption in rodents is its bitter taste, which is strongly aversive. Taste aversion is often overcome by the use of adulterants, such as sweeteners, to conceal morphine taste or bitterants in the alternative bottle to equalize aversion. However, the adulterants\u2019 presence is the cause for consumption choice and, upon removal, the preference for morphine is not preserved. Thus, current animal models are not suitable to study treatments aimed at reducing consumption elicited by morphine itself. Since taste preference is a learned behavior, just-weaned rats were trained to accept a bitter taste, adding the bitterant quinine to their drinking water for one week. The latter was followed by allowing the choice of quinine or morphine (0.15 mg\/mL) solutions for two weeks. Then, quinine was removed, and the preference for morphine against water was evaluated. Using this paradigm, we show that rats highly preferred the consumption of morphine over water, reaching a voluntary morphine intake of 15 mg\/kg\/day. Morphine consumption led to significant analgesia and hyperlocomotion, and to a marked deprivation syndrome following the administration of the opioid antagonist naloxone. Voluntary morphine consumption was also shown to generate brain oxidative stress and neuroinflammation, signs associated with opioid dependence development. We present a robust two-bottle choice animal model of oral morphine self-administration for the evaluation of therapeutic interventions for the treatment of morphine dependence.<\/jats:p>","DOI":"10.3390\/ijms23073874","type":"journal-article","created":{"date-parts":[[2022,3,31]],"date-time":"2022-03-31T21:34:29Z","timestamp":1648762469000},"page":"3874","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["A Novel Morphine Drinking Model of Opioid Dependence in Rats"],"prefix":"10.3390","volume":"23","author":[{"given":"Pablo","family":"Berr\u00edos-C\u00e1rcamo","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Quezada","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Santapau","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8914-2977","authenticated-orcid":false,"given":"Paola","family":"Morales","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Department of Neuroscience, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Research Center for the Development of Novel Therapeutic Alternatives for Alcohol Use Disorders, Santiago 8900000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bel\u00e9n","family":"Olivares","sequence":"additional","affiliation":[{"name":"Center for Medical Chemistry, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Ponce","sequence":"additional","affiliation":[{"name":"Faculty of Agricultural and Forestry Sciences, Universidad de la Frontera, Temuco 4811230, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alba","family":"\u00c1vila","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0231-2468","authenticated-orcid":false,"given":"Cristian","family":"De Gregorio","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Ezquer","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Elena","family":"Quintanilla","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6015-8334","authenticated-orcid":false,"given":"Mario","family":"Herrera-Marschitz","sequence":"additional","affiliation":[{"name":"Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3468-7966","authenticated-orcid":false,"given":"Yedy","family":"Israel","sequence":"additional","affiliation":[{"name":"Center for Regenerative Medicine, Faculty of Medicine Cl\u00ednica Alemana, Universidad del Desarrollo, Santiago 7610658, Chile"},{"name":"Molecular and Clinical Pharmacology Program, Institute of Biomedical Science, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile"},{"name":"Research Center for the Development of Novel Therapeutic Alternatives for Alcohol Use Disorders, Santiago 8900000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7696-4215","authenticated-orcid":false,"given":"Fernando","family":"Ezquer","sequence":"additional","affiliation":[{"name":"Center for 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