title: Neonatal sensitization to ethanol-induced breathing disruptions as a function of late prenatal exposure to the drug in the rat: modulatory effects of ethanol's chemosensory cues.
abstract: Preclinical and clinical studies have systematically demonstrated abrupt changes in fetal respiratory patterns when the unborn organism is exposed to the effects of maternal ethanol intoxication. In subprimates, chronic exposure to this drug during gestation and infancy results in marked alterations of the plasticity of the respiratory network. These alterations are manifested in terms of an early incapability to overcome deleterious effects of hypoxic events as well as in terms of sensitization to ethanol's depressant effects upon breathing patterns. It has also been demonstrated that near term rat fetuses process ethanol's chemosensory cues when the drug contaminates the amniotic fluid and that associative learning processes occur due to the temporal contiguity existing between these cues and different ethanol-related physiological effects. In the present study during the course of late gestation (gestational days 17-20), pregnant rats were intragastrically administered with either 0.0 or 2.0 g/kg ethanol. Seven-day-old pups derived of these dams were evaluated in terms of respiration rates (breaths/min) and apneas when subjected to different experimental conditions. These conditions were defined by postnatal exposure to the drug (intragastric administrations of either 0.0, 0.5, 1.0 or 2.0 g/kg ethanol), postadministration time of evaluation (5-10 or 30-35 min) and olfactory context at test (no explicit ambient odor or ethanol ambient odor). The results, obtained via whole body plethysmography, indicated that brief prenatal experience with the drug sensitized the organisms to ethanol's depressant effects particularly when employing the higher ethanol doses. In turn, presence of ethanol odor at test potentiated the above mentioned respiratory alterations. Prenatal treatment with ethanol was not found to alter pharmacokinetic profiles resulting from postnatal exposure to the drug or to affect different morphometric parameters related with lung development. These results indicate that even brief exposure to the drug during late gestation is sufficient to sensitize the organism to later disruptive effects of the drug upon breathing responsiveness. These deficits are potentiated through the re-exposure to the olfactory context perceived in utero which is known to be associated with ethanol's unconditioned effects. As a function of these observations it is possible to suggest a critical role of fetal sensory and learning capabilities in terms of modulating later ethanol-related breathing disruptions.
authors.affiliation: Instituto de Investigación Médica Mercedes y Martin Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Cullere
authors.affiliation: Instituto de Investigación Médica Mercedes y Martin Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Argentina.
authors.forename: Ana Fabiola
authors.initials: AF
authors.lastname: Macchione
authors.affiliation: Instituto de Investigación Médica Mercedes y Martin Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Argentina.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Haymal
authors.affiliation: Unidad Hospitalaria San Roque, Universidad Nacional de Córdoba, Argentina.
authors.forename: Martin
authors.initials: M
authors.lastname: Paradelo
authors.affiliation: Hospital Aeronáutico, Cordoba, Argentina.
authors.forename: Marcos Daniel
authors.initials: MD
authors.lastname: Langer
authors.affiliation: Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, USA. Electronic address: nspear@binghamton.edu.
authors.forename: Norman E
authors.initials: NE
authors.lastname: Spear
authors.affiliation: Instituto de Investigación Médica Mercedes y Martin Ferreyra, INIMEC-CONICET-Universidad Nacional de Córdoba, Argentina; Center for Development and Behavioral Neuroscience, Binghamton University, Binghamton, NY, USA; Facultad de Psicología, Universidad Nacional de Córdoba, Argentina. Electronic address: jmolina@immf.uncor.edu.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Molina
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000633:toxicity*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D008168:Lung / Q000187:drug effects / Q000254:growth & development / Q000503:physiopathology; D008297:Male; D009812:Odorants; D055696:Olfactory Perception / Q000187:drug effects* / Q000502:physiology*; D010993:Plethysmography, Whole Body; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: Breathing disruption; Fetal ethanol intoxication; Late gestation; Olfactory stimulation; Sensitization