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To examine the direct effects of serotonin (5-HT) on the release and synthesis of
corticotropin-releasing factor (CRF) in the hypothalamic paraventricular nucleus (PVN),
5-HT was microinjected just onto the bilateral PVN of conscious rats. Plasma adrenocorticotropic
hormone (ACTH) levels peaked at 30 min and returned to the basal levels in 90 min.
Northern blot analysis revealed that the CRF messenger RNA (mRNA) level in the PVN
as well as the proopiomelanocortin mRNA level in the anterior pituitary significantly
increased 120 min after the 5-HT injections (50-250 nmol/side). Pretreatment with
intracerebroventricular (i.c.v.) injection of pindobind 5-HT1A (5 nmol) or LY-278584
(500 nmol) completely abolished the 5-HT-induced ACTH response, whereas LY-53857 (100
nmol) was without effect. These results suggest that 5-HT stimulates CRF release,
which has interactions with 5-HT1A and 5-HT3 receptors on CRF neurons in the PVN,
and activates CRF synthesis in conscious rats.