Central stimulation of adrenocortical secretion by 5-hydroxytryptamine1A agonists is mediated by sympathomedullary activation.
The mechanism by which the 5-hydroxytryptamine1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) increases adrenocortical secretion was examined using treatments designed to alter the hypothalamo-pituitary-adrenocortical axis and the autonomic nervous system. Adrenocortical responses to peripherally administered 8-OH-DPAT were preserved in animals with radiofrequency lesions of the hypothalamic paraventricular nucleus or with posterior hypothalamic deafferentations. However, adrenocortical responses to 8-OH-DPAT were abolished in hypophysectomized animals, although both acute and chronic treatment with dexamethasone were without effect. The influence of catecholamines in the central and sympathetic nervous systems was investigated using treatments designed to alter central and peripheral catecholaminergic systems. Adrenocortical responses after intracerebroventricular administration of high doses of 8-OH-DPAT were attenuated by i.v. and intra-adrenal treatment with 6-hydroxydopamine (6-OHDA), by adrenal medullectomy, by splanchnicectomy and by combined 6-OHDA-sympathectomy/medullectomy. Responses to i.p. 8-OH-DPAT were only partially attenuated by medullectomy and by 6-OHDA-sympathectomy/medullectomy. The ganglionic blocking agent, chlorisondamine also blocked the adrenocortical response after intracerebroventricular, but not i.p., administration of 8-OH-DPAT. These effects did not appear to be due to surgical damage to the adrenal cortex because the operated animals showed normal adrenocortical responses to challenge with adrenocorticotropic hormone. The data obtained indicate that adrenocortical secretion in response to i.p. and intracerebroventricular administration of the 5-hydroxytryptamine1A receptor agonist 8-OH-DPAT largely involves a sympathomedullary activation, but that additional peripheral mechanisms are also involved after i.p. administration.
Saphier
D
D
Department of Pharmacology and Therapeutics, Louisiana State University Medical Center, Shreveport.
Welch
J E
JE
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000302:Adrenal Cortex / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D007016:Hypophysectomy; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism; D013153:Splanchnic Nerves / Q000502:physiology / Q000601:surgery; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology
D011985:Receptors, Serotonin; D015116:5,7-Dihydroxytryptamine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003907:Dexamethasone; D016627:Oxidopamine