title: Effects of acute ethanol exposure on anxiety measures and epigenetic modifiers in the extended amygdala of adolescent rats.
abstract: Epigenetic mechanisms appear to play an important role in neurodevelopment. We investigated the effects of acute ethanol exposure on anxiety measures and function of histone deacetylases (HDAC) and DNA methyltransferases (DNMT) in the amygdala and bed nucleus of stria terminalis (BNST) of adolescent rats. One hour after ethanol exposure, rats were subjected to anxiety measures. A subset of adolescent rats was exposed to two doses (24 h apart) of ethanol (2 g/kg) to measure rapid ethanol tolerance to anxiolysis. The HDAC and DNMT activities and mRNA levels of DNMT isoforms were measured in the amygdala and BNST. The lower dose of ethanol (1 g/kg) produced neither anxiolysis, nor inhibited the HDAC and DNMT activities in the amygdala and BNST, except DNMT activity in BNST was attenuated. Anxiolysis by ethanol was observed at 2 and 2.25 g/kg, whereas higher doses (2.5 and 3 g/kg) were found to be sedative. DNMT activity in the amygdala and BNST, and nuclear HDAC activity in the amygdala, but not in the BNST were also inhibited by these doses of ethanol. A lack of tolerance was observed on ethanol-induced inhibition of DNMT activity in the amygdala and BNST, and nuclear HDAC activity in the amygdala, as well to anxiolysis produced by ethanol (2 g/kg). The DNMT1, DNMT3a, and DNMT3b mRNA expression in the amygdala was not affected by either 1or 2 doses of 2 g/kg. However, DNMT1 and DNMT3a expression in the BNST was increased, whereas DNMT3l mRNA was decreased in the amygdala, after 2 doses of 2 g/kg ethanol. These results suggest that reduced sensitivity to anxiolysis and the lack of rapid tolerance to the anxiolytic effects of ethanol and inhibition of HDAC and DNMT functions may play a role in engaging adolescents in binge drinking patterns.
authors: Department of Psychiatry,University of Illinois at Chicago,Chicago, IL 60612,USA.
authors: Amul J
authors: AJ
authors: Sakharkar
authors: Department of Psychiatry,University of Illinois at Chicago,Chicago, IL 60612,USA.
authors: Lei
authors: L
authors: Tang
authors: Department of Psychiatry,University of Illinois at Chicago,Chicago, IL 60612,USA.
authors: Huaibo
authors: H
authors: Zhang
authors: Department of Psychiatry,University of Illinois at Chicago,Chicago, IL 60612,USA.
authors: Ying
authors: Y
authors: Chen
authors: Department of Psychiatry,University of Illinois at Chicago,Chicago, IL 60612,USA.
authors: Dennis R
authors: DR
authors: Grayson
authors: Department of Psychiatry,University of Illinois at Chicago,Chicago, IL 60612,USA.
authors: Subhash C
authors: SC
authors: Pandey
mesh_terms: D000679:Amygdala / Q000187:drug effects* / Q000254:growth & development / Q000503:physiopathology; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D004305:Dose-Response Relationship, Drug; D044127:Epigenesis, Genetic / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012686:Septal Nuclei / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D000097584:DNA Methyltransferase 3B
chemical_list: D002492:Central Nervous System Depressants; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000431:Ethanol; D006655:Histone Deacetylases; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000619382:Dnmt1 protein, rat