Fulton T Crews1, Christopher J Braun. 1. Bowles Center for Alcoholic Studies, University of North Carolina at Chapel Hill, Chapel Hill 27599-7178, USA. ftcrews@med.unc.edu
Abstract
BACKGROUND: Genetics is a known risk factor for alcoholism, and human alcoholics are known to suffer from a loss of brain function and mass. A 4 day rat binge drinking model is known to cause brain region-specific damage. To investigate the role of genetics in binge-drinking-induced brain damage, we studied bidirectionally selected rat lines, the alcohol-preferring P and the alcohol-nonpreferring NP rat lines. METHOD: P and NP rats were treated with a 4 day binge ethanol protocol. Animals were killed, transcardially perfused, and fixed, and their brains were removed, sectioned, and stained by using the amino cupric silver stain of de Olmos or by using immunohistochemistry for phospho-extracellular signal regulated kinases and other antigens. RESULTS: Significant brain damage was found in the olfactory bulbs, posterior perirhinal cortex, and entorhinal cortex in both P and NP rats. P rats were found to have significantly greater brain damage, compared with NP rats, in the posterior perirhinal and posterior entorhinal cortexes, 239% +/- 50% (p < 0.02) and 219% +/- 46% (p < 0.01), respectively. Phospho-extracellular signal regulated kinase immunohistochemistry stained prominently in damaged brain areas. CONCLUSIONS: The P rat line, a genetic model of alcoholism, shows greater region-specific brain damage due to binge ethanol treatment than its genetic counterpart, the NP rat line. These findings suggest that genetics contribute to susceptibility for binge-induced brain damage.
BACKGROUND: Genetics is a known risk factor for alcoholism, and human alcoholics are known to suffer from a loss of brain function and mass. A 4 day rat binge drinking model is known to cause brain region-specific damage. To investigate the role of genetics in binge-drinking-induced brain damage, we studied bidirectionally selected rat lines, the alcohol-preferring P and the alcohol-nonpreferring NP rat lines. METHOD: P and NP rats were treated with a 4 day binge ethanol protocol. Animals were killed, transcardially perfused, and fixed, and their brains were removed, sectioned, and stained by using the amino cupric silver stain of de Olmos or by using immunohistochemistry for phospho-extracellular signal regulated kinases and other antigens. RESULTS: Significant brain damage was found in the olfactory bulbs, posterior perirhinal cortex, and entorhinal cortex in both P and NP rats. P rats were found to have significantly greater brain damage, compared with NP rats, in the posterior perirhinal and posterior entorhinal cortexes, 239% +/- 50% (p < 0.02) and 219% +/- 46% (p < 0.01), respectively. Phospho-extracellular signal regulated kinase immunohistochemistry stained prominently in damaged brain areas. CONCLUSIONS: The P rat line, a genetic model of alcoholism, shows greater region-specific brain damage due to binge ethanol treatment than its genetic counterpart, the NP rat line. These findings suggest that genetics contribute to susceptibility for binge-induced brain damage.
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