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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.

Author information

1
Equipe Région INSERM-24 Groupe de Recherche sur l'Alcool et les Pharmacodèpendances, Facultè de Pharmacie, Amiens, France.

Abstract

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 facilitation.

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
DOI:
10.1164/rccm.200703-434OC
[Indexed for MEDLINE]

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