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
1 and
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
1 and
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