Perinatal alcohol exposure in rat induces long-term depression of respiration after episodic hypoxia.
BACKGROUND
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.


OBJECTIVE
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.


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.
Kervern
Myriam
M
Equipe Région INSERM-24 Groupe de Recherche sur l'Alcool et les Pharmacodèpendances, Facultè de Pharmacie, Amiens, France.
Dubois
Christophe
C
Naassila
Mickael
M
Daoust
Martine
M
Pierrefiche
Olivier
O
D000818:Animals; D000831:Animals, Newborn; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects*; D010991:Plethysmography; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A; D012119:Respiration / Q000187:drug effects*
D002492:Central Nervous System Depressants; D044282:Receptor, Serotonin, 5-HT1A; D000431:Ethanol