Midline B₃ serotonin nerves in rat medulla are involved in hypotensive effect of methyldopa

Previous experiments in this laboratory have shown that microinjection of methyldopa onto the ventrolateral cells of the B₃ serotonin neurons in the medulla elicits a hypotensive response mediated by a projection descending into the spinal cord. The present experiments were designed to investigate the role of the midline cells of the B₃ serotonin neurons in the medulla, coinciding with the raphe magnus. In spontaneously hypertensive, stroke-prone rats, microinjection of methyldopa into the area of the midline B₃ serotonin cell group in the ventral medulla caused a potent hypotension of 30-40 mm Hg, which was maximal 2-3 h after administration and was abolished by the serotonin neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) injected intracerebroventricularly. However, intraspinal injection of 5,7-DHT to produce a more selective lesion of only descending serotonin projections in the spinal cord did not affect this hypotension. Further, 5,7-DHT lesion of serotonin nerves travelling in the median forebrain bundle, one of the main ascending pathways from the B₃ serotonin cells, did not affect the fall in blood pressure associated with a midline B₃ serotonin methyldopa injection. It is concluded therefore that, unlike the ventrolateral B₃ cells which mediate a methyldopa-induced hypotension via descending projections, the midline serotonin B₃ cells in the medulla contribute to the hypotensive action of methyldopa, either by way of an ascending projection which does not pass through the median forebrain bundle, or through a projection restricted to the caudal brainstem.