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A growing concern is that prenatal exposure to opioids may induce persistent neurological changes that increase the propensity for future addictions. Although alcohol represents the most likely addictive substance that the growing population of prenatal opioid exposed will encounter as they mature, no studies to date have examined the effect of prenatal opioid exposure on future sensitivity to alcohol reward. Using a recently developed mouse model of prenatal methadone exposure (PME), we investigated the rewarding properties of alcohol and alcohol consumption in male and female adolescent PME and prenatal saline exposed (PSE) control animals. Conditioned place preference to alcohol was disrupted in PME offspring in a sex\u2010dependent manner with PME males exhibiting resistance to the rewarding properties of alcohol. Repeated injections of alcohol revealed enhanced sensitivity to the locomotor\u2010stimulating effects of alcohol specific to PME females. PME males consumed significantly more alcohol over 4\u2009weeks of alcohol access relative to PSE males and exhibited increased resistance to quinine\u2010adulterated alcohol. Further, a novel machine learning model was developed to employ measured differences in alcohol consumption and drinking microstructure to reliably predict prenatal exposure. These findings indicate that PME alters the sensitivity to alcohol reward in adolescent mice in a sex\u2010specific manner and suggests prenatal opioid exposure may induce persistent effects on reward neurocircuitry that can reprogram offspring behavioural response to alcohol later in life.<\/jats:p>","DOI":"10.1111\/adb.13136","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T09:50:24Z","timestamp":1642413024000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Prenatal opioid exposure reprograms the behavioural response to future alcohol reward"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-8633","authenticated-orcid":false,"given":"Gregory G.","family":"Grecco","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Indiana 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