Dopamine-beta-hydroxylase activity is necessary for hypothalamo-pituitary-adrenal (HPA) responses to ether, and stress-induced facilitation of subsequent HPA responses to acute ether emerges as HPA responses are inhibited by increasing corticosterone (B).
To determine a role of norepinephrine (NE) in stress-induced HPA function, young male rats were treated with diethyldithiocarbamide (DDC) which inhibits dopamine-beta-hydroxylase, the enzyme that synthesizes NE from dopamine (DA). DDC injected 5 h prior to ether stress stimulated ACTH and corticosterone (B) during this time, and there was no further HPA response to ether. To control for elevated B feedback in DDC effects on HPA responses to ether, rats were adrenalectomized (Adx) and replaced with no (0% B), moderate (40% B) and high (80% B) levels of steroid 5 d prior to DDC or saline with ether stress 5 h later; Sham-Adx rats were included. In Adx rats increasing B inhibited thymus weight, median eminence CRF content, pituitary and plasma ACTH. In saline-treated rats, ether 5 h later caused increased CRF content and plasma ACTH in Sham-Adx and Adx, 0% B, increased ACTH in Adx, 40% B, and no response in Adx, 80% B. B treatment did not alter catecholamine content, and DDC treatment reduced NE content in the paraventricular nuclei by 50-60% in all groups. 5 h after DDC, pituitary ACTH was decreased in all rats with B and plasma ACTH was increased in sham-Adx and Adx, 40% B; thus DDC caused significant, prolonged stress which should facilitate subsequent HPA responses to acute stress. There was no HPA response to ether in Sham-Adx, Adx, 0% or 40% B groups, but there was a marked ACTH response to ether in the Adx, 80% B group treated with DDC. We conclude that: 1) the HPA response to ether stress is probably mediated by catecholamines; 2) DDC does not stimulate responses in the HPA axis in the absence of B; and, 3) facilitation of HPA responses to acute stress depends on increased steady-state B signals. Facilitated responses are probably not mediated by catecholamines. The consequence of facilitation is that under conditions of chronic stress and elevated B concentrations, as in depression or anorexia nervosa in man, or adjuvent-induced arthritis in rats, the HPA axis is continually responsive to new stimuli.
Murakami
K
K
Department of Physiology, University of California San Francisco, 94143-0444, USA.
Akana
S F
SF
Dallman
M F
MF
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004050:Ditiocarb / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D004986:Ether / Q000494:pharmacology*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological
D004791:Enzyme Inhibitors; D004986:Ether; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D004050:Ditiocarb; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine; D003345:Corticosterone; D009638:Norepinephrine; D004837:Epinephrine