Sex differences and addiction severity influence methadone, buprenorphine, and naltrexone efficacy on oxycodone motivation in genetically diverse rat

Sex differences and addiction severity influence methadone, buprenorphine, and naltrexone efficacy on oxycodone motivation in genetically diverse rat | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 13 May 2025 V1 Latest version Share on Sex differences and addiction severity influence methadone, buprenorphine, and naltrexone efficacy on oxycodone motivation in genetically diverse rat Author : Marsida Kallupi [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174713608.89988727/v1 204 views 120 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background and Purpose: Opioid use disorder (OUD) is a major public health issue. Medications like buprenorphine, methadone, and naltrexone show variable efficacy in reducing opioid craving and use in humans. However, it is unclear if similar individual differences exist in animal models. This study investigated how sex and addiction severity impact these medications’ efficacy in genetically diverse rats. Experimental Approach: Over 500 heterogeneous stock rats underwent intermittent, extended oxycodone self-administration to establish dependence and escalation of intake. Acute effects of single doses of buprenorphine (0.5 mg/kg), methadone (3 mg/kg), and naltrexone (3 mg/kg) on the motivation of oxycodone self-administration were assessed using a progressive ratio schedule. Key Results: Naltrexone and buprenorphine significantly reduced oxycodone self-administration motivation. Naltrexone was effective in both sexes, while buprenorphine only reduced responses in males. Methadone showed no significant reduction across groups, though some rats with moderate to severe addiction-like behaviors displayed reduced responses. Naltrexone’s efficacy was independent of addiction severity, while buprenorphine was more effective in rats with moderate to severe addiction-like behaviors. Conclusions and Implications: This study demonstrates that, genetically diverse rats, like humans, show individual differences in OUD medication efficacy. Addiction severity influenced sensitivity to certain medications, emphasizing the need to consider individual differences in studying OUD’s neurobiological mechanisms and treatments. This study used single doses in an acute pretreatment paradigm; dose-response relationships and chronic treatment effects require further exploration. Supplementary Material File (oxy pharmacology 2025_mk_2.pdf) Download 1.20 MB Information & Authors Information Version history V1 Version 1 13 May 2025 Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords addiction behavioural pharmacology biological sex opioids translational pharmacology Authors Affiliations Marsida Kallupi [email protected] University of California San Diego View all articles by this author Metrics & Citations Metrics Article Usage 204 views 120 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Marsida Kallupi. Sex differences and addiction severity influence methadone, buprenorphine, and naltrexone efficacy on oxycodone motivation in genetically diverse rat. Authorea . 13 May 2025. DOI: https://doi.org/10.22541/au.174713608.89988727/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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