GABAA receptors mediate postnatal depression of respiratory frequency by barbiturates.
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 microM bicuculline methiodide, a GABAA receptor antagonist. Pentobarbital up to a concentration of 80 microM (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 GABAA 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.
Fregosi
Ralph F
RF
Department of Physiology, College of Medicine, The University of Arizona, Tucson, AZ 85721, USA. fregosi@u.arizona.edu
Luo
Zili
Z
Iizuka
Makito
M
D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D018682:GABA Agents / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D066298:In Vitro Techniques; D009118:Muscimol / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D012125:Respiratory Center / Q000187:drug effects*; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000503:physiopathology; D015656:Respiratory Mechanics / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects; D013126:Spinal Nerve Roots / Q000187:drug effects
D018682:GABA Agents; D006993:Hypnotics and Sedatives; D011963:Receptors, GABA-A; D009118:Muscimol; D010424:Pentobarbital; D001640:Bicuculline