The aim of this study was to determine the site in the CNS at which 5-hydroxytryptamine (5-HT) inhibits efferent sympathetic nerve activity in the cat. 5-Hydroxytryptamine (3 and 10 micrograms/kg), given into the lateral cerebral ventricle, produced immediate non dose related increases in mean blood pressure (MBP), heart rate (HR) and renal nerve activity (RNA). Larger doses (30 and 100 micrograms/kg i.c.v.) produced gradual decreases in blood pressure, heart rate and renal nerve activity, which did not occur when access of the drug to the fourth ventricle was prevented. Administration of 5-HT (10 and 30 micrograms/kg) into the fourth ventricle produced only decreases in blood pressure, heart rate and renal nerve activity after 15-40 min, which were accompanied by decreases in cardiac output and renal vascular resistance, but little or no change in total peripheral resistance. Application of 5-HT onto the ventral surface of the medulla, into the subarachnoid space at various levels along the spinal cord or into various parts of the nucleus tractus solitarius produced no effect on blood pressure heart rate or renal nerve activity. However, application of a cotton wool pledget soaked in a 5-HT solution (3 mg/ml) over the entire obex/NTS region produced immediate decreases in blood pressure, heart rate and renal nerve activity. These studies suggest that the sympatho-inhibitory effect of 5-HT is due to an action at a site near the caudal end of the dorsal surface of the medulla.
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