Medullary ventral surface GABA receptors affect respiratory and cardiovascular function

We previously demonstrated that GABA and muscimol administered either into the cisterna magna or the fourth ventricle to chloralose-anesthetized cats cause respiratory depression, hypotension, and bradycardia. Injection of these substances into the lateral and third ventricles had no effect. In order to localize the site of action, muscimol and GABA were applied by Perspex rings to the ventral surface of the medulla. Application of muscimol (0.25-2.66 micrograms) to Schlaefke's area in 6 cats reduced minute ventilation from 443 +/- 38 to 291 +/- 52 ml/min by reducing tidal volume from 31.8 +/- 2.3 to 17.6 +/- 1.4 ml, without changing respiratory rate and duration of inspiration. Hypotension and bradycardia were also observed. Application of GABA (0.14-4.86 mg) produced similar effects on respiratory activity and arterial blood pressure. No significant effects occurred when high doses of these agents were applied to Loeschcke's and Mitchell's areas. Application of bicuculline (5-25 micrograms) to Schlaefke's area had the opposite effect of muscimol and GABA on respiratory activity and blood pressure, and reversed the respiratory and cardiovascular depressant effects of both agents. We conclude that GABA receptors are present at Schlaefke's area, and that activation of these receptors results in respiratory depression, hypotension, and bradycardia. Our results suggest that GABA may be an important inhibitory neurotransmitter in the modulation of respiratory and cardiovascular control.