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Abstract
Serotonin-1A (5-HT1A) binding sites were previously localized in several regions of
the ventral medulla associated with neural regulation of the cardiovascular system.
Some of these binding sites were associated with serotonergic neurons of the ventral
medulla. The purpose of these studies was to assess and characterize hypotensive responses
to a 5-HT1A agonist, (8-hydroxy-dipropylaminotetraline, 8-OH-DPAT), administered to
the ventral medulla of the rat, to correlate the responsive ventral medullary sites
with the distribution of 3H-8-OH-DPAT binding sites, and to assess the role of serotonergic
systems in mediating the hypotensive responses. Ventral medullary application of 8-OH-DPAT
caused dose-related reductions in mean arterial pressure and heart rate which were
mediated by the autonomic nervous system. The hypotensive response to 8-OH-DPAT was
attenuated by pretreatment with the 5-HT1A antagonists, spiperone or NAN-190. Microinjections
of 8-OH-DPAT into ventral medullary structures revealed that 8-OH-DPAT responsive
sites included the raphe pallidus, the parapyramidal region, and the rostral ventrolateral
medulla. The role of serotonergic terminals in mediating the responses of 8-OH-DPAT
was evaluated in animals pretreated with the serotonin nerve toxin, 5,7-dihydroxytryptamine
(5,7-DHT). Cardiovascular responses to ventral medullary application of 8-OH-DPAT
were unaffected by the selective depletion of serotonin. Thus, whereas the hypotensive
responses elicited by 8-OH-DPAT in the raphe pallidus and parapyramidal region may
involve serotonergic neurons, other non-serotonergic sites (e.g. the rostral ventrolateral
medulla) can mediate the hypotensive actions of 8-OH-DPAT.