Blockade of forebrain gamma-aminobutyric acid (GABA) receptors and reflex activation of the cardiac vagus in anesthetized cats

gamma-Aminobutyric acid (GABA) antagonists have been shown to produce sympathetically mediated increases in blood pressure and heart rate when restricted to the forebrain cerebral ventricles of anesthetized cats. This study explored the possibility that similar administration of these agents might produce reciprocal effects on reflex cardiac vagal excitability. Drugs were infused into and restricted to the forebrain ventricles of cats anesthetized with chloralose and urethane. Arterial pressure and heart rate were continuously monitored and reproducible reflex vagal bradycardia was periodically elicited by bolus i.v. injections of phenylephrine. In early experiments in intact cats and in later studies in spinal transected animals, i.c.v. administration of the GABA antagonist bicuculline methiodide (1-32 micrograms) suppressed phenylephrine-induced reflex bradycardia in a dose-related fashion. When tested in spinal transected cats, i.c.v. picrotoxin, another GABA antagonist, mimicked this effect of bicuculline methiodide. Intraventricular muscimol (10 micrograms), a GABA agonist, had no effect in untreated cats but reversed the effects of bicuculline methiodide and picrotoxin. These data point to tonic GABAergic inhibition in the periventricular forebrain which suppresses the activity of a descending vagal inhibitory mechanism.