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Perinatal Alcohol Exposure in Rat Induces Long-Term Depression of Respiration after Episodic Hypoxia

¹ Equipe Région INSERM-24 Groupe de Recherche sur l'Alcool et les Pharmacodépendances, Faculté de Pharmacie, Amiens, France

Correspondence and requests for reprints should be addressed to Olivier Pierrefiche, Ph.D., ERI-24 GRAP, Faculté de Pharmacie, 1 rue des Louvels, 80036 Amiens. E-mail: op-lnc{at}u-picardie.fr

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.

Key Words: plasticity • respiratory depression • serotonin • ethanol

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Alcohol depresses respiration, but little is known about the effects of chronic alcohol exposure during pregnancy on respiratory long-term facilitation (LTF), induced after repeated hypoxic episodes. What This Study Adds to the Field Perinatal alcohol exposure in rats converts respiratory LTF into long-term depression. Alcohol exposure during pregnancy may therefore lead to long-term maladaptive behavior of the respiratory network in neonates in response to low oxygen.