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Nicotinic acetylcholine receptors (nAChRs) containing the \u03b16 and \u03b23 subunits are expressed in neural reward circuits and are critical for nicotine and alcohol reward. nAChRs are dynamically regulated by signaling molecules such as protein kinase C epsilon (PKC\u03b5), which impact transcription of \u03b16 and \u03b23 subunit mRNA (\n                    <jats:italic>Chrna6<\/jats:italic>\n                    and\n                    <jats:italic>Chrnb3<\/jats:italic>\n                    , respectively). Previous work found decreased expression of\n                    <jats:italic>Chrna6<\/jats:italic>\n                    and\n                    <jats:italic>Chrnb3<\/jats:italic>\n                    transcripts in the ventral midbrain of male PKC\u03b5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, who also consume less nicotine and alcohol compared with wild\u2010type (WT) littermates. Using RT\u2010qPCR, we show that female PKC\u03b5\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice have higher expression of\n                    <jats:italic>Chrna6<\/jats:italic>\n                    and\n                    <jats:italic>Chrnb3<\/jats:italic>\n                    transcripts in the ventral midbrain, which functionally impacts nAChR\u2010dependent behavior as female but not male PKC\u03b5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice exhibit locomotor hypersensitivity to low\u2010dose (0.25 mg\/kg i.p.) nicotine. Female PKC\u03b5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice show no differences in alcohol\u2010induced sedation in the loss\u2010of\u2010righting reflex assay (4.0 g\/kg i.p.) compared with WT littermates, whereas male PKC\u03b5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice have enhanced sedation compared with WT mice. Female PKC\u03b5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice also show reduced immobility time in response to varenicline (1.0 mg\/kg i.p.) compared with WT littermates in the tail suspension test, and this effect was absent in male mice. Additionally, we found that female PKC\u03b5\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice show altered alcohol and nicotine consumption patterns in chronic voluntary two\u2010bottle choice assays. Our data reveal a bidirectional effect of sex in the transcriptional regulation of nicotinic receptors by PKC\u03b5, highlighting the importance of studying both sexes in preclinical animal models.\n                  <\/jats:p>","DOI":"10.1111\/adb.12954","type":"journal-article","created":{"date-parts":[[2020,8,10]],"date-time":"2020-08-10T03:31:33Z","timestamp":1597030293000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Bidirectional sex\u2010dependent regulation of \u03b16 and \u03b23 nicotinic acetylcholine receptors by protein kinase C\u03b5"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6167-5472","authenticated-orcid":false,"given":"Janna K.","family":"Moen","sequence":"first","affiliation":[{"name":"Graduate Program in Neuroscience University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margot C.","family":"DeBaker","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julia E.","family":"Myjak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Wickman","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience University of Minnesota  Minneapolis Minnesota USA"},{"name":"Department of Pharmacology University of Minnesota  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4551-0082","authenticated-orcid":false,"given":"Anna M.","family":"Lee","sequence":"additional","affiliation":[{"name":"Graduate Program in Neuroscience University of Minnesota  Minneapolis Minnesota 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