Cognitive impairment and increased brain neurosteroids in adult rats perinatally exposed to low millimolar blood alcohol concentrations

Summary Epidemiological evidence suggests that adolescents and adults perinatally exposed to alcohol, even at low doses, show high prevalence of cognitive impairment and social behavior deficits, which may be in part related to alcohol-induced changes of the γ -aminobutyric acid (GABA)ergic neurotra...

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Bibliographic Details
Published in:Psychoneuroendocrinology 2007-09, Vol.32 (8), p.931-942
Main Authors: Barbaccia, Maria Luisa, Scaccianoce, Sergio, Del Bianco, Paola, Campolongo, Patrizia, Trezza, Viviana, Tattoli, Maria, Cuomo, Vincenzo, Steardo, Luca
Format: Article
Language:English
Subjects:
3 α-hydroxy-5 α-pregnan-20-one (allopregnanolone, 3 α,5 α-THP)
Alcohol Drinking - adverse effects
Animals
Animals, Newborn
Behavior, Animal - drug effects
Behavioral psychophysiology
Biological and medical sciences
Brain Chemistry - drug effects
Cognition Disorders - blood
Cognition Disorders - chemically induced
Developmental alcohol
Elevated-plus maze
Endocrinology & Metabolism
Ethanol - blood
Ethanol - pharmacology
Female
Fundamental and applied biological sciences. Psychology
Hormones and behavior
Inhibitory avoidance
Lactation - drug effects
Male
Pregnancy
Prenatal Exposure Delayed Effects - blood
Prenatal Exposure Delayed Effects - psychology
Progesterone
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Rats
Rats, Wistar
Reproduction - drug effects
Social recognition memory
Steroids - analysis
Steroids - blood
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Summary:Summary Epidemiological evidence suggests that adolescents and adults perinatally exposed to alcohol, even at low doses, show high prevalence of cognitive impairment and social behavior deficits, which may be in part related to alcohol-induced changes of the γ -aminobutyric acid (GABA)ergic neurotransmission. The endogenous neurosteroid 3 α -hydroxy,5 α -pregnan-20-one (3 α ,5 α -tetrahydroprogesterone/3 α ,5 α -THP), a potent positive allosteric modulator of GABAA receptor function, is implicated in the physiological tuning of GABA-mediated fast inhibition and in various alcohol's actions in the brain. This study was undertaken to determine whether perinatal exposure to low millimolar blood alcohol concentrations alters cognitive skills (social discrimination and inhibitory avoidance tests), emotional reactivity (elevated plus maze test), and neurosteroid content in brain cortex and hippocampus of adult male offspring. Dams had access to a 3% alcohol solution or to an equicaloric sucrose solution from gestational day 15 to postnatal day 9. Eighty-day old alcohol-exposed male offspring exhibited impaired social recognition memory, but unchanged inhibitory avoidance performance and normal behavior on the elevated-plus maze. The concentrations of 3 α ,5 α -THP and its precursor progesterone were more than doubled in brain cortex and hippocampus of alcohol-exposed rats, whereas in plasma only progesterone was increased. Thus, exposure to low millimolar blood alcohol concentrations has a long-lasting impact on the developing brain as it causes an impairment of social recognition as well as an increase of brain neurosteroid content in mature animals. The latter may be consequent to altered expression/activity of brain steroidogenic enzymes, as reflected by the enduring increase of the GABAA receptor-active neurosteroid 3 α ,5 α -THP in brain cortex and hippocampus, but not in plasma. It is speculated that, by inducing a greater amplification of GABAA receptor function, the elevation of 3 α ,5 α -THP brain content contributes to the cognitive impairment exhibited by adult alcohol-exposed offspring.
ISSN:0306-4530
1873-3360
DOI:10.1016/j.psyneuen.2007.06.013