title: Gene expression changes in serotonin, GABA-A receptors, neuropeptides and ion channels in the dorsal raphe nucleus of adolescent alcohol-preferring (P) rats following binge-like alcohol drinking.
abstract: Alcohol binge-drinking during adolescence is a serious public health concern with long-term consequences. We used RNA sequencing to assess the effects of excessive adolescent ethanol binge-drinking on gene expression in the dorsal raphe nucleus (DRN) of alcohol preferring (P) rats. Repeated binges across adolescence (three 1h sessions across the dark-cycle per day, 5 days per week for 3 weeks starting at 28 days of age; ethanol intakes of 2.5-3 g/kg/session) significantly altered the expression of approximately one-third of the detected genes. Multiple neurotransmitter systems were altered, with the largest changes in the serotonin system (21 of 23 serotonin-related genes showed decreased expression) and GABA-A receptors (8 decreased and 2 increased). Multiple neuropeptide systems were also altered, with changes in the neuropeptide Y and corticotropin-releasing hormone systems similar to those associated with increased drinking and decreased resistance to stress. There was increased expression of 21 of 32 genes for potassium channels. Expression of downstream targets of CREB signaling was increased. There were also changes in expression of genes involved in inflammatory processes, axonal guidance, growth factors, transcription factors, and several intracellular signaling pathways. These widespread changes indicate that excessive binge drinking during adolescence alters the functioning of the DRN and likely its modulation of many regions of the central nervous system, including the mesocorticolimbic system.
authors.affiliation: Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United States; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: Jeanette N
authors.initials: JN
authors.lastname: McClintick
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Ding
authors.affiliation: Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United States; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN 46202, United States.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.affiliation: Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, United States; Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, IN 46202, United States; Department of Medical & Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, United States. Electronic address: edenberg@iu.edu.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
mesh_terms: D000428:Alcohol Drinking; D000818:Animals; D065847:Dorsal Raphe Nucleus / Q000378:metabolism*; D020869:Gene Expression Profiling; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D009479:Neuropeptides; D011963:Receptors, GABA-A; D012701:Serotonin
keywords: Alcoholism; CREB; GABA-A receptors; Inflammation; Neuropeptides; Serotonin