The Effects of Short-Term Chronic Ethanol Intoxication and Ethanol Withdrawal on the Molecular Composition of the Rat Hippocampus by FT-IR Spectroscopy
Article first published online: 1 JUN 2011
Copyright © 2011 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 35, Issue 11, pages 2050–2062, November 2011
How to Cite
Elibol-Can, B., Jakubowska-Dogru, E., Severcan, M. and Severcan, F. (2011), The Effects of Short-Term Chronic Ethanol Intoxication and Ethanol Withdrawal on the Molecular Composition of the Rat Hippocampus by FT-IR Spectroscopy. Alcoholism: Clinical and Experimental Research, 35: 2050–2062. doi: 10.1111/j.1530-0277.2011.01556.x
- Issue published online: 1 NOV 2011
- Article first published online: 1 JUN 2011
- Received for publication June 22, 2010; accepted March 19, 2011.
- Ethanol Abuse;
- Ethanol Withdrawal;
- FT-IR Spectroscopy
Background: The numerous adverse effects of ethanol abuse and ethanol withdrawal on biological systems are well documented. Conversely, the understanding of the molecular mechanisms underlying these pathological effects is still incomplete. This study was undertaken to investigate the effects of short-term chronic ethanol administration and ethanol withdrawal on the molecular structure and function of hippocampal tissue, a brain region important for mnemonic processes and known to be highly susceptible to ethanol intoxication.
Methods: Ethanol was administered to adult Wistar rats by intragastric intubation for 15 days with a stepwise increase in the daily dose from 6 to 12 g/kg body weight, with the highest dose delivered for the last 2 days only. The total daily dose of ethanol was divided into 3 equal portions administered 4 hours apart. Animals were sacrificed by decapitation at 4, 24, and 72 hours after the last ethanol administration to examine potential effects of ethanol intoxication and ethanol withdrawal. Ethanol-related molecular changes were monitored by Fourier transform infrared (FT-IR) spectroscopy.
Results: Significant changes in the hippocampal content, structure, and function of lipids, proteins, and nucleic acids were recorded under ethanol intoxication. Seventy-two hours after the cessation of ethanol administration, during the late phase of withdrawal, alterations in the macromolecules’ content and conformational changes in protein and nucleic acid structure ameliorated, while the changes in macromolecular ratios, lipid order, and dynamics aggravated.
Conclusions: Our results suggest that 15 days of binge-like drinking resulting in the high blood alcohol concentration (varying in the dose-dependent manner between 253 and 606 mg/dl) produced a strong physical dependence manifested mainly by the changes in lipid profiles pointing toward withdrawal-induced oxidative stress. These results show that ethanol withdrawal may cause equal to or even more severe brain damage than the ethanol itself, which should be considered when designing antialcohol therapies.