Central sites involved in the hypotensive effects of muscimol

Abstract

Areas within the brain mediating the hypotensive effects of muscimol, a GABA receptor agonist, were localized in chloralose anesthetized cats. Infusion of muscimol (0.003-0.03 μg/kg/min) into the lateral ventricle for 30 min resulted in a dose-related fall in blood pressure, heart rate and renal sympathetic nerve discharge when the perfusate was collected at the cisterna magna (ICV). Under these conditions the largest dose produced decreases in blood pressure, heart rate and renal nerve discharge of 40%, 30% and 80% respectively. When bicuculline methiodide (0.5 μg/kg/min), a GABA receptor antagonist, was administered via the cerebral aqueduct simultaneously with the ICV infusion of muscimol, the cardiovascular effects of muscimol were antagonized. Infusion of bicuculline methiodide alone failed to alter blood pressure or heart rate. When muscimol was prevented from reaching the fourth ventricle by collecting the perfusate at the caudal end of the cerebral aqueduct, the largest dose produced a reduction in blood pressure and heart of <15%. Administration of muscimol into the caudal region of the fourth ventricle failed to alter blood pressure, heart rate or renal nerve discharge. In contrast, administration of muscimol into the anterior region of the fourth ventricle produced large reductions in blood pressure and heart rate. These results indicate that the major sites mediating the hypotensive actions of muscimol are located in the anterior region or anteroventral surface of the medulla with a small contribution stemming from supra-medullary sites.