Evidence for a mutual interaction between noradrenergic and serotonergic agonists in stimulation of ACTH and corticosterone secretion in the rat

We investigated the mutual interactions between hypothalamic norepinephrine (NE) and serotonin (5-HT) in mediating the ACTH and corticosterone responses to direct stimulation of the paraventricular nucleus (PVN) with adrenergic and serotonergic agonists. The hormone responses to the intrahypothalamic injection of the alpha1-adrenergic agonist phenylephrine (20 nmol/2 microl) were significantly reduced by prior depletion of hypothalamic 5-HT with intra-PVN injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), but not after depletion of hypothalamic NE by intra-PVN injection of the noradrenergic neurotoxin 6-hydroxydopamine (6-OHDA). The ACTH and corticosterone responses to intrahypothalamic injection of the 5-HT(1A) receptor agonist 8-OH-DPAT (20 n mol/2 microl) were significantly reduced by depletion of hypothalamic NE with 6-OHDA, but not after depletion of hypothalamic 5-HT with 5,7-DHT. These mutual interactions between the NE and 5-HT neuronal systems, which innervate the PVN, may explain previous findings of equivalent reductions in the hypothalamic-pituitary-adrenal axis responses to neural stimulation after neurotoxic lesioning of either the NE or 5-HT systems.