PMID- 27503149 OWN - NLM STAT- MEDLINE DCOM- 20180118 LR - 20181113 IS - 1872-7549 (Electronic) IS - 0166-4328 (Print) IS - 0166-4328 (Linking) VI - 314 DP - 2016 Nov 1 TI - A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats. PG - 199-214 LID - S0166-4328(16)30492-2 [pii] LID - 10.1016/j.bbr.2016.07.054 [doi] AB - Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy drinking, and provokes oxidative brain damage. Here, we investigated whether the cerebellum and hippocampus of female rats are less affected by prooxidant EW than male rats due to the antioxidant effect of 17beta-estradiol (E2). Female and male rats received a four-week ethanol diet and three-week withdrawal per cycle for two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus (water-maze)-related behaviors, oxidative markers (O2(-), malondialdehyde, protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were subjected to ethanol-exposure and withdrawal for two cycles to assess the effect of a CcO inhibitor on E2's protection for mitochondrial respiration and cell viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative markers in cerebellum and hippocampus than male rats, and E2 treatment decreased the oxidative markers. Compared to male counterparts, ethanol-withdrawn female rats showed better Rotarod but poorer water-maze performance, accompanied by more severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or antioxidant treatment improved Rotarod but not water-maze performance. In the presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial respiration and cell viability from EW. These data suggest that antioxidant E2 contributes to smaller oxidative stress in ethanol-withdrawn female than male rats. They also suggest that EW-induced severe mitochondrial damage in hippocampus may blunt E2's antioxidant protection for hippocampus-related behavior. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Jung, Marianna E AU - Jung ME AD - Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA. Electronic address: Marianna.Jung@unthsc.edu. FAU - Metzger, Daniel B AU - Metzger DB AD - Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd., Fort Worth, TX 76107-2699, USA. LA - eng GR - R01 AA015982/AA/NIAAA NIH HHS/United States GR - R21 AA018747/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160805 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Antioxidants) RN - 0 (Reactive Oxygen Species) RN - 3K9958V90M (Ethanol) RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Antioxidants/pharmacology MH - Estradiol/pharmacology MH - Ethanol/*pharmacology MH - Female MH - Male MH - Mice MH - Mitochondria/drug effects/metabolism MH - Oxidative Stress/*drug effects MH - Rats, Sprague-Dawley MH - Reactive Oxygen Species/metabolism MH - *Sex Characteristics MH - Substance Withdrawal Syndrome/*metabolism PMC - PMC5002225 MID - NIHMS809951 OTO - NOTNLM OT - 17beta-Estradiol OT - Antioxidant OT - Cerebellum OT - Cytochrome c oxidase OT - Ethanol withdrawal OT - Hippocampus EDAT- 2016/08/10 06:00 MHDA- 2018/01/19 06:00 PMCR- 2017/11/01 CRDT- 2016/08/10 06:00 PHST- 2016/05/19 00:00 [received] PHST- 2016/07/25 00:00 [revised] PHST- 2016/07/30 00:00 [accepted] PHST- 2016/08/10 06:00 [entrez] PHST- 2016/08/10 06:00 [pubmed] PHST- 2018/01/19 06:00 [medline] PHST- 2017/11/01 00:00 [pmc-release] AID - S0166-4328(16)30492-2 [pii] AID - 10.1016/j.bbr.2016.07.054 [doi] PST - ppublish SO - Behav Brain Res. 2016 Nov 1;314:199-214. doi: 10.1016/j.bbr.2016.07.054. Epub 2016 Aug 5.