{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:47:02Z","timestamp":1768783622243,"version":"3.49.0"},"reference-count":57,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,7]],"date-time":"2023-01-07T00:00:00Z","timestamp":1673049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU)","award":["NeuroCompOpioid_PI2RL_IINFACTS_2021"],"award-info":[{"award-number":["NeuroCompOpioid_PI2RL_IINFACTS_2021"]}]},{"name":"Cooperativa de Ensino Superior Polit\u00e9cnico e Universit\u00e1rio (CESPU)","award":["CBToxAtOpi-GI2-CESPU-2022"],"award-info":[{"award-number":["CBToxAtOpi-GI2-CESPU-2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Tramadol and tapentadol, synthetic opioids commonly prescribed for moderate-to-severe pain, have a unique pharmacology that optimizes their analgesia and safety. However, they are not devoid of risks, presenting addictive, abuse, and dependence potential. While tramadol-reinforcing properties have been documented by various studies with human and animal models, including conditioned place preference (CPP) assays, no similar studies have been performed with tapentadol. In the present study, we performed CPP assays by intraperitoneally administering Wistar rats with a tramadol\/tapentadol therapeutic dose. Animal permanence and the number of entries in the CPP compartments were recorded in the preconditioning phase and then 1 (T1), 7 (T7), and 14 (T14) days after conditioning. Both opioids induced a change in place preference (T1), suggesting that they have short-term reinforcing properties. However, only tramadol was associated with place preference retention (T7 and T14), with an increase in the number of entries in the opioid-paired compartment (T1 and T7), showing that it causes rewarding memory and incubation of craving. The results indicate that at therapeutic doses: (1) both drugs cause short-term rewarding effects and (2) as opposed to tramadol, tapentadol does not cause CPP retention, despite its higher central nervous system activity and stricter scheduling.<\/jats:p>","DOI":"10.3390\/ph16010086","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T07:28:10Z","timestamp":1673249290000},"page":"86","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Tramadol and Tapentadol Induce Conditioned Place Preference with a Differential Impact on Rewarding Memory and Incubation of Craving"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-1029","authenticated-orcid":false,"given":"Joana","family":"Barbosa","sequence":"first","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences\u2014CESPU (IUCS-CESPU), 4585-116 Gandra, PRD, Portugal"},{"name":"UCIBIO-REQUIMTE\u2014Applied Molecular Biosciences Unit-Network of Chemistry and Technology, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6762-4534","authenticated-orcid":false,"given":"Sandra","family":"Leal","sequence":"additional","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences\u2014CESPU (IUCS-CESPU), 4585-116 Gandra, PRD, Portugal"},{"name":"CINTESIS@RISE\u2014Center for Health Technology and Services Research of the Health Research Network, MEDCIDS\u2014Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, Rua Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9381-3320","authenticated-orcid":false,"given":"Frederico C.","family":"Pereira","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Experimental Therapeutics\/iCBR\u2014Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7430-6297","authenticated-orcid":false,"given":"Ricardo Jorge","family":"Dinis-Oliveira","sequence":"additional","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences\u2014CESPU (IUCS-CESPU), 4585-116 Gandra, PRD, Portugal"},{"name":"UCIBIO-REQUIMTE\u2014Applied Molecular Biosciences Unit-Network of Chemistry and Technology, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"Department of Public Health and Forensic Sciences, and Medical Education, Faculty of Medicine, University of Porto, 4099-002 Porto, Portugal"},{"name":"MTG Research and Development Lab, 4200-604 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7753-0219","authenticated-orcid":false,"given":"Juliana","family":"Faria","sequence":"additional","affiliation":[{"name":"TOXRUN\u2014Toxicology Research Unit, University Institute of Health Sciences\u2014CESPU (IUCS-CESPU), 4585-116 Gandra, PRD, Portugal"},{"name":"UCIBIO-REQUIMTE\u2014Applied Molecular Biosciences Unit-Network of Chemistry and Technology, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101198","DOI":"10.1016\/j.eclinm.2021.101198","article-title":"Global consumption of prescription opioid analgesics between 2009\u20132019: A country-level observational study","volume":"42","author":"Jayawardana","year":"2021","journal-title":"EClinicalMedicine"},{"key":"ref_2","first-page":"31","article-title":"Utilization, Spending, and Price of Opioid Medications in the US Medicaid Programs Between 1991 and 2019","volume":"15","author":"Alsultan","year":"2022","journal-title":"Am. 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