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

Abstract

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 GABA A receptors and relative protein levels for GABA A 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 Ϯ 55 mg/dl (71.3 Ϯ 12.0 mM) on gestational day 57 (term, ϳ68 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 [ 3 H]muscimol binding sites was increased in adult offspring from the ethanol treatment group, and there was a corresponding increase in the amount of GABA A 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 GABA A receptor neurochemistry. There was no effect of chronic prenatal ethanol exposure on [ 3 H]MK-801 binding in this tissue. These data demonstrate that chronic prenatal ethanol exposure has long-term consequences on the regulation of GABA A receptor expression in the cerebral cortex.

Acute sensitivity and acute tolerance to ethanol in preweanling rats with or without prenatal experience with the drug

“…anxiety or depression). This neuroendocrinological alteration seems to be accompanied by changes in neurotransmitter systems that not only participate in stress regulation but also modulate ethanol's positive as well as negative (anti-anxiety) reinforcing properties (Bailey, Brien, & Reynolds, 2001;Druse, Tajuddin, Kuo, & Connerty, 1990;Sari & Zhou, 2004). Furthermore, chronic exposure during gestation to large ethanol doses has also been observed to modify acute sensitivity to different ethanol's effects.…”

Increased ethanol intake after prenatal ethanol exposure: Studies with animals

“…Prenatal ethanol exposure may also alter other neurochemical systems which may in turn directly or indirectly modulate the unconditioned effects of ethanol and its voluntary consumption. For instance, chronic prenatal ethanol exposure has long-term effects on the regulation of GABA(A) receptor expression in the cerebral cortex (Bailey et al, 2001), and reduces the number of serotoninergic neurons (Sari and Zhou, 2004). This treatment has also been found to affect the normal development of the opioid system (McGivern et al, 1984;Shoemaker et al, 1983).…”

Prenatal exposure to an NMDA receptor antagonist, MK-801 reduces density of parvalbumin-immunoreactive GABAergic neurons in the medial prefrontal cortex and enhances phencyclidine-induced hyperlocomotion but not behavioral sensitization to methamphetamine in postpubertal rats

“…Additionally, prenatal exposure to ethanol, which not only stimulates GABA A receptors but also blocks NMDA receptors (Ikonomidou et al 2000), leads to long-lasting deficits of GABAergic interneurons in rat prefrontal cortex and increased spontaneous locomotor activity in adult offspring (Moore et al 1998;Bailey et al 2001). Glutamate plays, via NMDA receptors, an important role in the migration of immature neurons (Komuro and Rakic 1993;Behar et al 1999;Csillik et al 2002).…”