Early Ethanol Preexposure Modifies Expression of the 5HT2A Receptor Promoting Long-Term Breathing Plasticity in Neonate Rats

Abstract

EtOH´s effects upon respiration are attributed to central respiratory network disruptions, especially in the medullary serotonin (5HT) system. 5HT2A/2C receptors are involved in the reduction of the phrenic nerve activity and breathing depression. We hypothesize that early EtOH preexposure alters neonatal respiration through the 5HT system´s plasticity. Here, we evaluated breathing rates and the relative expression of 5HT 2A and 2C receptors in the brainstem as a function of EtOH preexposure in neonates. Pups received i.g administrations of 2.0 or 0.0g/kg EtOH at postnatal days (PD) 3, 5 and 7. At PD 9, breathing frequencies were recorded under normoxia or hypoxia. Brainstems were collected to quantified relative mRNA expression of 5HT 2A and 2C receptors, by qPCR. Under normoxia, EtOH preexposed pups (preEtOH) exhibited high 5HT2A expression levels and breathing depressions. An opposite phenomenon was observed in preEtOH pups tested under hypoxia. An exacerbated hyperventilation associated with low 5HT2A expression levels was found. No significant differences were found in 5HT2C expression levels. These results together with our previous findings that show changes in the raphe obscurus activation patterns, suggest that a brief EtOH preexposure is enough to induce 5HT system?s plasticity, disturbing neonatal breathing. The 5HT components mismatch may be associated with breathing disruptions commonly observed in human neonates, such as Sudden Infant Death Syndrome.