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The Journal of Neuroscience, June 15, 2001, 21(12):4381-4389

Chronic Prenatal Ethanol Exposure Increases GABAA Receptor Subunit Protein Expression in the Adult Guinea Pig Cerebral Cortex

Craig D. C. Bailey, James F. Brien, and James N. Reynolds

Department of Pharmacology and Toxicology, Faculty of Health Sciences, Queen's University, Kingston, Ontario, Canada K7L 3N6

Excessive consumption of ethanol during pregnancy can produce teratogenic effects in offspring and is the leading cause of mental deficiency in the Western world. The objective of this study was to examine the effects of chronic prenatal ethanol exposure on the number of GABAA receptors and relative protein levels for GABAA receptor alpha 1 and beta 2/3 subunits in the adult guinea pig cerebral cortex. Timed pregnant Dunkin-Hartley strain guinea pigs were given one of the following oral treatments daily throughout gestation: 4 gm of ethanol per kilogram of maternal body weight, isocaloric-sucrose with pair feeding, or isovolumetric water with ad libitum access to food. The ethanol treatment resulted in a peak maternal blood ethanol concentration of 328 ± 55 mg/dl (71.3 ± 12.0 mM) on gestational day 57 (term, ~68 d). Chronic prenatal exposure to ethanol resulted in increased spontaneous locomotor activity throughout development and decreased cerebral cortical weight in adult offspring. The number of cerebral cortical [3H]muscimol binding sites was increased in adult offspring from the ethanol treatment group, and there was a corresponding increase in the amount of GABAA receptor alpha 1 and beta 2/3 subunit proteins in these same animals. For individual offspring, there were correlations between locomotor activity and cerebral cortical weight, as well as between cerebral cortical weight and GABAA receptor neurochemistry. There was no effect of chronic prenatal ethanol exposure on [3H]MK-801 binding in this tissue. These data demonstrate that chronic prenatal ethanol exposure has long-term consequences on the regulation of GABAA receptor expression in the cerebral cortex.

Key words: GABAA receptor; NMDA receptor; prenatal ethanol exposure; cerebral cortex; guinea pig; radioligand binding; Western blot


Copyright © 2001 Society for Neuroscience  0270-6474/01/21124381-09$05.00/0


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J. Physiol., October 1, 2006; 576(1): 297 - 307.
[Abstract] [Full Text] [PDF]



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