Bulbospinal serotonin pressor pathways and hypotensive action of methyldopa in the rat.

Abstract

The administration of methyldopa (200 mg/kg i.p.) induced a green fluorescence typical of catecholamine fluorescence, in regions of the brain stem which coincided with all the major serotonin cell groups, including the B1, B2, and B3 cell groups in the medulla. Prior administration of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin relatively specific for serotonin neurons, prevented the appearance of this methyldopa-induced fluorescence. Electrical stimulation of the ventrolateral medulla in areas that coincided with the lateral elements of the B1 and B3 serotonin cell groups evoked pressor responses recorded via cannulae in the abdominal aorta. The pressor responses were frequency-dependent and could be markedly attenuated by prior administration of 5,7-DHT either intracerebroventricularly (i.c.v.) or directly into the cervical cord to ablate descending serotonin nerve fibers. Microinjection of methyldopa (4-16 micrograms) directly into the region of the B1 and B3 cells in the ventrolateral medulla evoked a dose-dependent fall in arterial pressure observed for 4 hours. Here too, prior administration of 5,7-DHT either intracerebroventricularly or directly into the cervical cord largely prevented the hypotensive action of the microinjections of methyldopa. The administration of 5,7-DHT produced a highly selective depletion of serotonin stores without reducing the concentrations of norepinephrine. These experiments suggest that the activity of serotonin nerves descending into the spinal cord from the B1 and B3 cells in the ventrolateral medulla serves to elevate or maintain arterial pressure. They also suggest that these descending serotonin neurons may contribute to the hypotensive action of methyldopa.