Early ethanol pre-exposure alters breathing patterns by disruptions in the central respiratory network and serotonergic balance in neonate rats.

Early ethanol exposure alters neonatal breathing plasticity. Respiratory EtOH's effects are attributed to central respiratory network disruptions, particularly in the medullary serotonin (5HT) system. In this study we evaluated the effects of neonatal pre-exposure to low/moderate doses upon breathing rates, activation patterns of brainstem's nuclei and expression of 5HT 2A and 2C receptors. At PD9, breathing frequencies, tidal volumes and apneas were examined in pups pre-exposed to vehicle or ethanol (2.0 g/kg) at PDs 3, 5 and 7. This developmental stage is equivalent to the 3rd human gestational trimester, characterized by increased levels of synaptogenesis. Pups were tested under sobriety or under the state of ethanol intoxication and when subjected to normoxia or hypoxia. Number of c-Fos and 5HT immunolabelled cells and relative mRNA expression of 5HT 2A and 2C receptors were quantified in the brainstem. Under normoxia, ethanol pre-exposed pups exhibited breathing depressions and a high number of apneas. An opposite phenomenon was found in ethanol pre-treated pups tested under hypoxia where an exacerbated hypoxic ventilatory response (HVR) was observed. The breathing depression was associated with an increase in the neural activation levels of the raphe obscurus (ROb) and a high mRNA expression of the 5HT 2A receptor in the brainstem while desactivation of the ROb and high activation levels in the solitary tract nucleus and area postrema were associated to the exacerbated HVR. In summary, early ethanol experience induces respiratory disruptions indicative of sensitization processes. Neuroadaptive changes in central respiratory areas under consideration appear to be strongly associated with changes in their respiratory plasticity.

Temporal dissociation between sodium depletion and sodium appetite appearance: Involvement of inhibitory and stimulatory signals.

Our aim was to analyze the participation of inhibitory and stimulatory signals in the temporal dissociation between sodium depletion (SD) induced by peritoneal dialysis (PD) and the appearance of sodium appetite (SA), particularly 2h after PD, when the rats are hypovolemic/natremic but SA is not evident. We investigated the effects of bilateral injections of the serotonin (5-HT) receptor antagonist, methysergide, into the lateral parabrachial nucleus (LPBN) on hypertonic NaCl and water intake 2h vs. 24h after PD. We also studied plasma renin activity (PRA) and aldosterone (ALDO) concentration 2h vs. 24h after PD. Additionally, we combined the analysis of brain Fos immunoreactivity (Fos-ir) with the detection of double immunoreactivity in 5HT and oxytocinergic (OT) cells 2h after PD. Bilateral LPBN injections of methysergide (4µg/200nl at each site) increased NaCl intake when tested 2h after PD compared to controls. We found a significant increase in PRA and ALDO concentration after PD but no differences between 2 and 24h after PD. We also found for the first time a significant increase 2h after PD in the number of Fos-ir neurons in the brainstem nuclei that have been shown to be involved in the inhibition of SA. In summary, the results show that 5HT-mechanisms in the LPBN modulate sodium intake during the delay of SA when the renin angiotensin aldosterone system (RAAS) is increased. In addition, the activation of brainstem areas previously associated with the satiety phase of SA is in part responsible for the temporal dissociation between SD and behavioral arousal.