080 - Depressed respiratory response to hypoxia and increased central glycinergic inhibitions in a rat model of fetal alcohol syndrom - 05/12/08

Introduction: Environmental conditions during pregnancy may have profound effects on breathing. However, nothing is known about fetal alcohol exposure on respiratory adaptation to chemosensory challenges in the offspring while the deleterious effects of alcohol on CNS development are well described. We recently found that fetal alcohol exposure in rat slowed respiratory frequency in juvenile rats and that brainstem respiratory network became insensitive to GABA_A agonist <sup>[1J Physiol, 2006, 576, 297-307.

Cliquez ici pour aller à la section Références]</sup>. We now investigated both in vivo and in situ the respiratory response to low oxygen level and studied the role of glycinergic inhibitions.

Methods: Female rats had a 10% (v/v) ethanol solution as sole source of fluid for 4 weeks before mating, during gestation and lactation periods. We used 3 week-old offspring rats and measured breathing in vivo with plethysmography both in normal condition of oxygenation and during hypoxia (10% O₂). In an in situ perfused heart-brainstem preparation, we recorded phrenic nerve activity and its response to anoxia. Strychnine, a glycine receptor antagonist, was applied into the perfusate in a dose-dependent manner. Anoxia was tested again in presence of strychnine. <sup>[1J Physiol, 2006, 576, 297-307.

Cliquez ici pour aller à la section Références]</sup> H]strychnine binding experiments were performed at the level of the brainstem. Heart and lungs were dissected and weights while blood samples were collected to assess for oxygen blood status.

Results: The response to hypoxia was abolished in vivo and phrenic nerve response to anoxia was reduced while gasping activity was unaffected in situ. In situ, strychnine applications demonstrated a high sensitivity of expiratory duration during normal oxygenation. Indeed, 0.2µM strychnine compensated the lower basal phrenic nerve frequency and also the response to anoxia. [³H]strychnine binding experiments showed an increase in both Bmax and Kd. Heart and lungs developed normally after birth, and polycythemia was detected.

These results demonstrate that ethanol exposure during brain growth spurt period in rat induced polycythemia, possibly to compensate the low respiratory frequency at rest, and increased glycinergic inhibitions within the central respiratory network that was responsible for the blunted response to low oxygen.

Conclusion: Exposure to ethanol during gestation and/or early life compromises respiratory chemoreflex in juvenile offspring and may possibly put the neonates at risk.