Brief ethanol exposure and stress-related factors disorganize neonatal breathing plasticity during the brain growth spurt period in the rat

Abstract

Rationale: The effects of early ethanol exposure upon neonatal respiratory plasticity have received progressive attention given a multifactorial perspective related with sudden infant death syndrome or hypoxia-associated syndromes. The present preclinical study was performed in 3–9-day-old pups, a stage in development characterized by a brain growth spurt that partially overlaps with the 3rd human gestational trimester. Methods: Breathing frequencies and apneas were examined in pups receiving vehicle or a relatively moderate ethanol dose (2.0 g/kg) utilizing a whole body plethysmograph. The experimental design also considered possible associations between drug administration stress and exteroceptive cues (plethysmographic context or an artificial odor). Ethanol exposure progressively exerted a detrimental effect upon breathing frequencies. A test conducted at PD9 when pups were under the state of sobriety confirmed ethanol’s detrimental effects upon respiratory plasticity (breathing depression). Results: Pre-exposure to the drug also resulted in a highly disorganized respiratory response following a hypoxic event, i.e., heightened apneic episodes. Associative processes involving drug administration procedures and placement in the plethysmographic context also affected respiratory plasticity. Pups that experienced intragastric administrations in close temporal contiguity with such a context showed diminished hyperventilation during hypoxia. In a 2nd test conducted at PD9 while pups were intoxicated and undergoing hypoxia, an attenuated hyperventilatory response was observed. In this test, there were also indications that prior ethanol exposure depressed breathing frequencies during hypoxia and a recovery normoxia phase. Conclusion: As a whole, the results demonstrated that brief ethanol experience and stress-related factors significantly disorganize respiratory patterns as well as arousal responses linked to hypoxia in neonatal rats.