Serotonin and Metabolic Ethanol Effects on Ventilatory Response to Intermittent Hypoxia in Rat Neonates

Abstract

Early EtOH high/acute doses diminish hypoxic ventilatory response and serotonin-5HT levels in the medullary 5HT- system. Yet, differential effects of EtOH pre-exposure from those of acute EtOH intoxication during delivery/neonatal period have not been studied. Here, we studied whether EtOH pre-exposure together or not with an acute EtOH intoxication alters ventilatory, metabolic and neurochemistry response against an intermittent hypoxic challenge (IH).At postnatal days-PD 3, 5and 7, pups were pre-exposed to EtOH or vehicle (2.0 or 0.0g/kg, ig). At PD9, pups were EtOH re-intoxicated or not (vehicle-administered) and all pups were subjected to a IH protocol (O 2 8%). Respiratory frequencies (fR) were recorded in a whole body plethysmograph. After, brains and blood samples were collected. 5TH-neurons in medullary raphe nuclei and metabolic hypoxemia/hypercapnia parameters we reassessed. Results showed that acute EtOH intoxication depressed breathing, particularly during hypoxic events, independentlyfrom EtOH pre-exposure. Yet, in sober pups, EtOH-exposure increased fRs during hypoxic events. After IH, acute EtOH- intoxication induced a metabolic acidosis-hypercapnia but EtOH pre-exposure increased pO 2 ,SO% and COHb/oxyHb ratio. Any form of EtOH exposure increased 5HT levels in medullary raphe nuclei analyzed. In summary, EtOH pre-exposure induces different effects from those generated by acute intoxication itself. In acute, respiratory depression with hypercapnia/acidosis was found. However, EtOH pre-exposure improves ventilatory andoxygenation patterns. Probably, acute intoxication masks EtOH pre-exposure effects, which are only appearing under sobriety. However, any form of drug experience increases 5HTlevels in the medullary raphe nuclei.