GABAA receptors mediate postnatal depression of respiratory frequency by barbiturates

Ralph F. Fregosi, Zili Luo, Makito Iizuka

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

We tested the hypothesis that barbiturates depress respiratory motor output by actions on the GABAA receptor. We examined the influence of pentobarbital sodium on nerve activity recorded from a fourth cervical (C4) ventral root (phrenic motoneuron output) in the in vitro brainstem-spinal cord preparation of neonatal rats aged 1-3 days. Bath application of pentobarbital slowed the respiratory rhythm but this effect could be reversed by drug washout or by simultaneous application of 8 μM bicuculline methiodide, a GABA A receptor antagonist. Pentobarbital up to a concentration of 80 μM (or 20 mg/l) did not change the magnitude of C4 nerve bursts. The GABAA receptor agonist muscimol evoked similar changes. The results support the hypothesis that respiratory depression by barbiturates is due to GABAA receptor-mediated inhibition, with the principal effects on rhythm generation. In the light of recent studies suggesting that GABA A receptors may be excitatory in the early neonatal period, we examined postnatal changes in the GABAergic slowing of respiratory rhythm. Stimulation of GABAA receptors slowed respiratory rhythm from the first postnatal day, with no change in efficacy over the first 3 days of life.

Original languageEnglish (US)
Pages (from-to)219-230
Number of pages12
JournalRespiratory Physiology and Neurobiology
Volume140
Issue number3
DOIs
StatePublished - Jun 25 2004

Keywords

  • Control of breathing, respiratory motor output
  • Mammals, rat
  • Pattern of breathing, central rhythm
  • Receptor, GABA

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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