Evidence for the presence of a tonically active forebrain gaba system influencing central sympathetic outflow in the cat

Bicuculline administered into the lateral cerebral ventricle of chloralose-anesthetized cats produces increases in arterial pressure and heart rate. To determine whether this effect is localized to forebrain areas, bicuculline in doses of 1, 5 and 25 μg was administered into either the lateral and third ventricles with cannulation of the cerebral aqueduct, or into the fourth ventricle of vagotomized cats. Administration into the lateral and third ventricles resulted in dose-dependent increases in pressure and rate, with the maximal response being 63 ± 11 mm Hg and 44 ± 9 beats/min, respectively. These same doses when administered into the fourth ventricle had no significant effect on heart rate and only a slight effect on pressure. Administration of the GABA receptor agonist, muscimol, into the lateral and third ventricles in a dose that had no effect alone on pressure and rate (10 μg) prevented the cardiovascular effects of bicuculline. In contrast, administration of the centrally-active antihypertensive agent, clonidine (31 μg), had no effect on bicuculline-induced increases in pressure and rate. In addition, muscimol (10 μg), when administered at the time of the peak pressure and rate responses of bicuculline, restored these indices of cardiovascular function to normal. Clonidine (31 μg), however, administered in the same fashion had no effect. These results suggest that a tonically-active GABAergic system exists in the region of the forebrain and exerts inhibitory control over sympathetic activity influencing arterial pressure and heart rate.