Effects of GABAB receptor agonists and antagonists on the bulbar respiratory network in cat.
We examined the involvement of the GABAB receptor in central respiratory mechanisms. Respiratory neurons (RNs) from the ventral respiratory group in the medulla of the cat were subjected to iontophoretic applications of the GABAB receptor agonist baclofen and the antagonists saclofen and CGP 35348. In all types of RNs baclofen decreased the firing rate. This reduction was antagonized by CGP 35348. Application of either antagonist increased the spontaneous discharge in both inspiratory and expiratory RNs. CGP 35348 excited 57% of the neurons tested, on the average by 34% with ejection currents of 100 nA. Saclofen excited 6 of 9 neurons tested. Baclofen administered systemically (8-12 mg/kg i.v.) to either anesthetized, decerebrate or intact freely moving cats, induced a selective lengthening of the inspiratory phase, an effect comparable to the apneusis induced by the NMDA antagonist MK-801. Baclofen also produced either a pronounced decrease in the amplitude of phrenic nerve discharge or an apnea, both of which were reversed by increasing paCO2. The results suggest that endogenously released GABA acting on GABAB receptors may be involved in the control of respiratory neuronal discharge.
Institut Alfred Fessard, CNRS, Gif-sur-Yvette, France.
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D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D002415:Cats; D003655:Decerebrate State; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005110:Extracellular Space / Q000502:physiology; D058787:GABA-A Receptor Antagonists; D007478:Iontophoresis; D008526:Medulla Oblongata / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology; D010991:Plethysmography; D011963:Receptors, GABA-A / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000494:pharmacology
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; C066430:CGP 35348; D001418:Baclofen; C080629:saclofen