Blunted response to low oxygen of rat respiratory network after perinatal ethanol exposure: involvement of inhibitory control.
Acute ethanol depresses respiration, but little is known about chronic ethanol exposure during gestation and breathing, while the deleterious effects of ethanol on CNS development have been clearly described. In a recent study we demonstrated that pre- and postnatal ethanol exposure induced low minute ventilation in juvenile rats. The present study analysed in juvenile rats the respiratory response to hypoxia in vivo by plethysmography and the phrenic (Phr) nerve response to ischaemia in situ. Glycinergic neurotransmission was assessed in situ with strychnine application and [(3)H]strychnine binding experiments performed in the medulla. After chronic ethanol exposure, hyperventilation during hypoxia was blunted in vivo. In situ Phr nerve response to ischaemia was also impaired, while gasping activity occurred earlier and recovery was delayed. Strychnine applications in situ (0.05-0.5 microM) demonstrated a higher sensitivity of expiratory duration in ethanol-exposed animals compared to control animals. Moreover, [(3)H]strychnine binding density was increased after ethanol and was associated with higher affinity. Furthermore, 0.2 microM strychnine in ethanol-exposed animals restored the low basal Phr nerve frequency, but also the Phr nerve response to ischaemia and the time to recovery, while gasping activity appeared even earlier with a higher frequency. Polycythaemia was present after ethanol exposure whereas lung and heart weights were not altered. We conclude that chronic ethanol exposure during rat brain development (i) induced polycythaemia to compensate for low minute ventilation at rest; (ii) impaired the respiratory network adaptive response to low oxygen because of an increase in central glycinergic tonic inhibitions, and (iii) did not affect gasping mechanisms. We suggest that ethanol exposure during early life can be a risk factor for the newborn respiratory adaptive mechanisms to a low oxygen environment.
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Equipe Région INSERM ERI-24 GRAP, Groupe de Recherche sur l'Alcool et Pharmacodépendances, UFR de Pharmacie, 1, rue des Louvels, 80036 Amiens, France.
Houchi
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H
Naassila
M
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Daoust
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Pierrefiche
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O
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000009:adverse effects / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011042:Poisons / Q000494:pharmacology; D011086:Polycythemia / Q000503:physiopathology; D011188:Potassium / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology
D002492:Central Nervous System Depressants; D011042:Poisons; D000431:Ethanol; D013331:Strychnine; D011188:Potassium; D010100:Oxygen