Early chronic ethanol exposure in rats disturbs respiratory network activity and increases sensitivity to ethanol

C. Dubois, M. Naassila, M. Daoust, O. Pierrefiche
The Journal of Physiology. 2006-09-22; 576(1): 297-307
DOI: 10.1113/jphysiol.2006.111138

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Chronic ethanol exposure during the fetal period alters spontaneous neuronal
discharge, excitatory and inhibitory amino acid neurotransmission and neuronal
sensitivity to ethanol in the adult brain. However, nothing is known about the
effects of such exposure on the central respiratory rhythmic network, which is
highly dependent on ethanol-sensitive amino acid neurotransmission. In 3- to
4-week-old rats, we investigated (1) the effects of chronic ethanol exposure (10%
v/v as only source of fluid) during gestation and lactation on phrenic (Phr) and
hypoglossal (XII) nerve activity using an in situ preparation and on spontaneous
breathing at rest in unanaesthetized animals using plethysmography; (2) the
sensitivity of the respiratory system to ethanol re-exposure in situ; and (3) the
phrenic nerve response to muscimol, a GABA(A) receptor agonist, applied
systemically in an in situ preparation. In control rats, ethanol (10-80 mm)
induced a concentration-dependent decrease in the amplitude of both XII and Phr
motor outflows. At 80 mm ethanol, the amplitude of the activity of the two nerves
displayed a difference in sensitivity to ethanol and respiratory frequency
increased as a result of shortening of postinspiratory duration period. After
chronic ethanol exposure, respiratory frequency was significantly reduced by 43%
in situ and by 23% in unanaesthetized animals, as a result of a selective
increase in expiratory duration. During Phr burst, the ramp was steeper,
revealing modification of inspiratory patterning. Interestingly that re-exposure
to ethanol in situ elicited a dramatic inhibitory effect. At 80 mm, ethanol
abolished rhythmic XII nerve outflow in all cases and Phr nerve outflow in only
50% of cases. Furthermore, administration of 50 microm muscimol abolished Phr
nerve activity in all control rats, but only in 50% of ethanol-exposed animals.
Our results demonstrate that chronic ethanol exposure at an early stage of brain
development depresses breathing in juvenile rats, and sensitizes the respiratory
network to re-exposure to ethanol, which does not seem to involve GABAergic

DOI: 10.1113/jphysiol.2006.111138
PMCID: PMC1995622
PMID: 16857714 [Indexed for MEDLINE]

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