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.
Weidenfeld
Joseph
J
Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah University Hospital and Hebrew University-Hadassah Medical School, POB 12000, Jerusalem 91120, Israel. newman@hadassah.org
Feldman
Shaul
S
Itzik
Anna
A
Van de Kar
Louis D
LD
Newman
Michael E
ME
D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D018663:Adrenergic Agents; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism*; D004347:Drug Interactions; D009638:Norepinephrine / Q000378:metabolism*; D016627:Oxidopamine; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018663:Adrenergic Agents; D000316:Adrenergic alpha-Agonists; D018490:Serotonin Agents; D017366:Serotonin Receptor Agonists; D010656:Phenylephrine; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D016627:Oxidopamine; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D009638:Norepinephrine