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However, there is minimal knowledge of the effects of chronic alcohol processes on rhythmic circadian gene expression across brain regions important for circadian biology and alcohol intake. Therefore, the present study sought to test the effects of chronic binge-like drinking on diurnal circadian gene expression patterns in the master circadian pacemaker (SCN), the ventral tegmental area (VTA), and the nucleus accumbens (NAc) in High Drinking in the Dark-1 (HDID-1) mice, a unique genetic risk model for drinking to intoxication. Consistent with earlier findings, we found that 8 weeks of binge-like drinking reduced the amplitude of several core circadian clock genes in the NAc and SCN, but not the VTA. To better inform the use of circadian-relevant pharmacotherapies in reducing harmful drinking and ameliorating alcohol\u2019s effects on circadian gene expression, we tested whether the casein kinase-1 inhibitor, PF-67046, or the phosphodiesterase type-4 (an upstream regulator of circadian signalling) inhibitor, apremilast, would reduce binge-like intake and mitigate circadian gene suppression. PF-67046 did not reduce intake but did have circadian gene effects. In contrast, apremilast reduced drinking, but had no effect on circadian expression patterns.<\/jats:p>","DOI":"10.3390\/ijms231911084","type":"journal-article","created":{"date-parts":[[2022,9,22]],"date-time":"2022-09-22T01:47:06Z","timestamp":1663811226000},"page":"11084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Targeting the Maladaptive Effects of Binge Drinking on Circadian Gene Expression"],"prefix":"10.3390","volume":"23","author":[{"given":"Kolter","family":"Grigsby","sequence":"first","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9855-1043","authenticated-orcid":false,"given":"Courtney","family":"Ledford","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanvi","family":"Batish","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snigdha","family":"Kanadibhotla","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delaney","family":"Smith","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Firsick","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Tran","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayla","family":"Townsley","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaylee-Abril Vasquez","family":"Reyes","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"LeBlanc","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Ozburn","sequence":"additional","affiliation":[{"name":"Portland Veterans Affairs Medical Center, Research and Development Service, Portland, OR 97239, USA"},{"name":"Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/S0140-6736(19)31775-1","article-title":"Alcohol use disorders","volume":"394","author":"Carvalho","year":"2019","journal-title":"Lancet"},{"key":"ref_2","first-page":"135","article-title":"The risks associated with alcohol use and alcoholism","volume":"34","author":"Rehm","year":"2011","journal-title":"Alcohol Res. 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