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While numerous animal models have facilitated understanding of the consequences of excessive drinking, translational models allow for experimental manipulation of factors thought to contribute to AUD liability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We employ a single\u2010exposure conditioned place preference assay (SE\u2010CPP) to investigate the influence of age, sex and the opioid peptide \u03b2\u2010endorphin (bE) on the initial rewarding effects of ethanol, a strong predictor of AUDs. Adolescent (PND28\u201035) and adult (PND70\u201090) male and female, control C57BL\/6J and bE\u2010deficient mice were tested following a single injection of 1.5\u2009g\/kg of ethanol. Following the SE\u2010CPP test, animals were deeply anesthetized, sacrificed, and perfused, and the brains were subsequently sectioned at 40 microns and processed for immunohistochemical localization of c\u2010fos. One\u2010sample, two\u2010tailed <jats:italic>t<\/jats:italic>\u2010tests were used to assess drug preference or aversion and the locomotor effects of alcohol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In general, adults were more sensitive to the effects of alcohol than adolescents, and outcomes depended on sex and bE. For example, among females, adolescents were stimulated by the drug, but insensitive to locomotor effects as adults, while among males, adolescents were insensitive and adults sedated. Wild\u2010type adolescents of both sexes failed to evince initial subjective reward from the drug, but bE\u2010deficient adolescents, and all adult subjects, preferred a context once associated with ethanol over one that had been paired with saline. c\u2010fos immunoreactivity in multiple brain regions was attenuated in bE\u2010deficient animals, though influences of both sex and bE grew stronger with age.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study demonstrates the utility of the SE\u2010CPP paradigm for elucidating factors that contribute to the liability for AUDs, and supports the growing body of research that shows that sensitivity to the rewarding effects of alcohol changes during the course of development. Our results also suggest that developmental contributions are sex\u2010dependent, and may also depend on the influence of endogenous opioid signaling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.15281","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T08:48:35Z","timestamp":1709282915000},"page":"667-679","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Sensitivity to the initial rewarding effects of alcohol: Influence of age, sex, and \u03b2\u2010endorphin"],"prefix":"10.1111","volume":"48","author":[{"given":"Madison A.","family":"Waldron","sequence":"first","affiliation":[{"name":"Department of Psychology, Neuroscience Program Bucknell University  Lewisburg Pennsylvania USA"},{"name":"Department of Neuroscience University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly 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