Perinatal Alcohol Exposure in Rat Induces Long-Term Depression of Respiration after Episodic Hypoxia
Am J Respir Crit Care Med. 2009-04-01; 179(7): 608-614
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1. Am J Respir Crit Care Med. 2009 Apr 1;179(7):608-14. doi:
10.1164/rccm.200703-434OC. Epub 2008 Dec 23.
Perinatal alcohol exposure in rat induces long-term depression of respiration
after episodic hypoxia.
Kervern M(1), Dubois C, Naassila M, Daoust M, Pierrefiche O.
(1)Equipe Région INSERM-24 Groupe de Recherche sur l’Alcool et les
Pharmacodèpendances, Facultè de Pharmacie, Amiens, France.
RATIONALE: Little is known about the effects of alcohol exposure during
pregnancy, which is responsible for fetal alcohol syndrome and the respiratory
network functions, especially respiratory network plasticity (e.g., long-term
facilitation) elicited after repeated short-lasting hypoxic episodes. The
mechanism of induction of respiratory long-term facilitation involves 5-HT(2A/2C)
receptors, which also participate in the response to hypoxia. Because fetal
alcohol exposure is known to reduce serotonin centrally, and synaptic plasticity
in the hippocampus, we hypothesized that alcohol exposure during gestation might
impair respiratory long-term facilitation after hypoxic episodes.
OBJECTIVES: To analyze the effects of prenatal and postnatal alcohol exposure on
respiratory long-term facilitation in 5- to 7-day-old rats.
METHODS: Respiratory frequency and amplitude were measured in vivo and in an in
vitro rhythmic medullary slice before and after three hypoxia episodes or three
applications of a 5-HT(2A/2C) receptor agonist in vitro. 5-HT(2A/2C) receptor
mRNA was measured from the slice.
MEASUREMENTS AND MAIN RESULTS: Alcohol exposure impaired respiratory long-term
facilitation and induced long-term depression of respiration in both in vivo and
in vitro models. Alcohol altered 5-HT(2A/2C) mRNA expression, although
5-HT(2A/2C) agonist efficacy was not altered in increasing rhythmic activity in
slices. However, a higher concentration of 5-HT(2A/2C) agonist was necessary to
induce transient facilitation in slices from ethanol-exposed animals, suggesting
disturbances in induction and maintenance mechanisms of respiratory long-term
CONCLUSIONS: Respiratory facilitation after repeated hypoxia was converted to
long-term depression in rats treated with alcohol in utero. Alcohol exposure
during pregnancy may therefore induce long-term maladaptive behavior of the
respiratory system in neonates.
PMID: 19106308 [Indexed for MEDLINE]