title: Changes in gene expression within the extended amygdala following binge-like alcohol drinking by adolescent alcohol-preferring (P) rats.
abstract: The objective of this study was to determine changes in gene expression within the extended amygdala following binge-like alcohol drinking by male adolescent alcohol-preferring (P) rats. Starting at 28 days of age, P rats were given concurrent access to 15 and 30% ethanol for 3 one-h sessions/day for 5 consecutive days/week for 3 weeks. Rats were killed by decapitation 3 h after the first ethanol access session on the 15th day of drinking. RNA was prepared from micropunch samples of the nucleus accumbens shell (Acb-sh) and central nucleus of the amygdala (CeA). Ethanol intakes were 2.5-3.0 g/kg/session. There were 154 and 182 unique named genes that significantly differed (FDR=0.2) between the water and ethanol group in the Acb-sh and CeA, respectively. Gene Ontology (GO) analyses indicated that adolescent binge drinking produced changes in biological processes involved with cell proliferation and regulation of cellular structure in the Acb-sh, and in neuron projection and positive regulation of cellular organization in the CeA. Ingenuity Pathway Analysis indicated that, in the Acb-sh, there were several major intracellular signaling pathways (e.g., cAMP-mediated and protein kinase A signaling pathways) altered by adolescent drinking, with 3-fold more genes up-regulated than down-regulated in the alcohol group. The cAMP-mediated signaling system was also up-regulated in the CeA of the alcohol group. Weighted gene co-expression network analysis indicated significant G-protein coupled receptor signaling and transmembrane receptor protein kinase signaling categories in the Acb-sh and CeA, respectively. Overall, the results of this study indicated that binge-like alcohol drinking by adolescent P rats is differentially altering the expression of genes in the Acb-sh and CeA, some of which are involved in intracellular signaling pathways and may produce changes in neuronal function.
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States. Electronic address: wmcbride@iupui.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Kimpel
authors.affiliation: Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States; Center for Medical Genomics, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, 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, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States.
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Ding
authors.affiliation: Department of Biochemistry & Molecular Biology, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States; Center for Medical Genomics, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States.
authors.forename: Tiebing
authors.initials: T
authors.lastname: Liang
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States.
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, Indianapolis, IN 46202, United States.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
mesh_terms: D000428:Alcohol Drinking; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051381:Rats
chemical_list: D000431:Ethanol
keywords: Adolescent binge drinking; Alcohol-preferring rat; Central nucleus of the amygdala; Gene expression; Nucleus accumbens-shell