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This study investigated whether hypothalamic proopiomelanocortin (<jats:styled-content style=\"fixed-case\">POMC<\/jats:styled-content>) neurons (producing beta\u2010endorphin and melanocortins) play a role in alcohol drinking behaviors. Both male and female mice with targeted deletion of two neuronal<jats:italic>Pomc<\/jats:italic>enhancers<jats:styled-content style=\"fixed-case\">nPE1<\/jats:styled-content>and<jats:styled-content style=\"fixed-case\">nPE2<\/jats:styled-content>(<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>\u2212\/\u2212), resulting in hypothalamic\u2010specific<jats:styled-content style=\"fixed-case\">POMC<\/jats:styled-content>deficiency, were studied in short\u2010access (4\u2010h\/day) drinking\u2010in\u2010the\u2010dark (<jats:styled-content style=\"fixed-case\">DID<\/jats:styled-content>, alcohol in one bottle, intermittent access (<jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>, 24\u2010h cycles of alcohol access every other day, alcohol vs. water in a two\u2010bottle choice) and alcohol deprivation effect (<jats:styled-content style=\"fixed-case\">ADE<\/jats:styled-content>) models. Wild\u2010type<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>+\/+ exposed to 1\u2010week<jats:styled-content style=\"fixed-case\">DID<\/jats:styled-content>rapidly established stable alcohol drinking behavior with more intake in females, whereas<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>\u2212\/\u2212 mice of both sexes had less intake and less preference. Although<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>\u2212\/\u2212 showed less saccharin intake and preference than<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>+\/+, there was no genotype difference in sucrose intake or preference in the<jats:styled-content style=\"fixed-case\">DID<\/jats:styled-content>paradigm. After 3\u2010week<jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>+\/+ gradually escalated to high alcohol intake and preference, with more intake in females, whereas<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>\u2212\/\u2212 showed less escalation. Pharmacological blockade of mu\u2010opioid receptors with naltrexone reduced intake in<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>+\/+ in a dose\u2010dependent manner, but had blunted effects in<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>\u2212\/\u2212 of both sexes. When alcohol was presented again after 1\u2010week abstinence from<jats:styled-content style=\"fixed-case\">IA<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>+\/+ of both sexes displayed significant increases in alcohol intake (<jats:styled-content style=\"fixed-case\">ADE<\/jats:styled-content>or relapse\u2010like drinking), with more pronounced<jats:styled-content style=\"fixed-case\">ADE<\/jats:styled-content>in females, whereas<jats:styled-content style=\"fixed-case\">nPE<\/jats:styled-content>\u2212\/\u2212 did not show<jats:styled-content style=\"fixed-case\">ADE<\/jats:styled-content>in either sex. Our results suggest that neuronal<jats:styled-content style=\"fixed-case\">POMC<\/jats:styled-content>is involved in modulation of alcohol \u2018binge\u2019 drinking, escalation and \u2018relapse\u2019, probably via hypothalamic\u2010mediated mechanisms, with sex differences.<\/jats:p>","DOI":"10.1111\/gbb.12362","type":"journal-article","created":{"date-parts":[[2016,11,21]],"date-time":"2016-11-21T14:45:07Z","timestamp":1479739507000},"page":"449-461","source":"Crossref","is-referenced-by-count":20,"title":["Hypothalamic\u2010specific proopiomelanocortin deficiency reduces alcohol drinking in male and female mice"],"prefix":"10.1111","volume":"16","author":[{"given":"Y.","family":"Zhou","sequence":"first","affiliation":[{"name":"Laboratory of the Biology of Addictive Diseases The Rockefeller University New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Rubinstein","sequence":"additional","affiliation":[{"name":"INGEBI\/CONICET University of Buenos Aires Buenos Aires Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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