title: Chronic prenatal ethanol exposure alters glucocorticoid signalling in the hippocampus of the postnatal Guinea pig.
abstract: The present study tested the hypothesis that chronic prenatal ethanol exposure causes long-lasting changes in glucocorticoid signalling in postnatal offspring. Pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight/day), isocaloric-sucrose/pair-feeding or water throughout gestation, and maternal saliva cortisol concentration was determined 2 h after treatment at different stages of gestation. Electrically-stimulated release of glutamate and GABA, in the presence or absence of dexamethasone, as well as glucocorticoid and mineralocorticoid receptor mRNA expression, was determined in the hippocampus and prefrontal cortex of adult offspring of treated pregnant guinea pigs. Maternal saliva cortisol concentration increased throughout pregnancy, which was associated with increased foetal plasma and amniotic fluid cortisol concentration. Ethanol administration to pregnant guinea pigs increased maternal saliva cortisol concentration during early and mid-gestation. In late gestation, ethanol administration did not increase saliva cortisol concentration above that induced by pregnancy. Chronic prenatal ethanol exposure had no effect on stimulated glutamate or GABA release, but selectively prevented dexamethasone-mediated suppression of stimulated glutamate release, and decreased expression of mineralocorticoid, but not glucocorticoid, receptor mRNA in the hippocampus of adult offspring. These data indicate that maternal ethanol administration leads to excessively increased maternal cortisol concentration that can impact negatively the developing foetal brain, leading to persistent postnatal deficits in glucocorticoid regulation of glutamate signalling in the adult hippocampus.
authors.affiliation: Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
authors.forename: U
authors.initials: U
authors.lastname: Iqbal
authors.forename: J F
authors.initials: JF
authors.lastname: Brien
authors.forename: S
authors.initials: S
authors.lastname: Banjanin
authors.forename: M H
authors.initials: MH
authors.lastname: Andrews
authors.forename: S G
authors.initials: SG
authors.lastname: Matthews
authors.forename: J N
authors.initials: JN
authors.lastname: Reynolds
mesh_terms: D000653:Amniotic Fluid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002940:Circadian Rhythm / Q000502:physiology; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005938:Glucocorticoids / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006854:Hydrocortisone / Q000378:metabolism; D017403:In Situ Hybridization; D008431:Maternal-Fetal Exchange; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000187:drug effects; D012463:Saliva / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002492:Central Nervous System Depressants; D005938:Glucocorticoids; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000431:Ethanol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D006854:Hydrocortisone