DOPAMINE-BETA-HYDROXYLASE ACTIVITY IS NECESSARY FOR HYPOTHALAMO-PITUITARY-ADRENAL (HPA) RESPONSES TO ETHER, AND STRESS-INDUCED FACILITATIONOF 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 funct ion, young male rats were treated with diethyldithiocarbamide (DDC) wh ich 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 furthe r HPA response to ether. To control for elevated B feedback in DDC eff ects on HPA responses to ether, rats were adrenalectomized (Adx) and r eplaced with no (0% B), moderate (40% B) and high (80% B) levels of st eroid 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-tre ated rats, ether 5 h later caused increased CRF content and plasma ACT H in Sham-Adx and Adx, 0%B, increased ACTH in Adx, 40%8, and no respon se 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; t hus DDC caused significant, prolonged stress which should facilitate s ubsequent 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 ACT H response to ether in the Adx, 80%8 group treated with DDC. We conclu de that: 1) the HPA response to ether stress is probably mediated by c atecholamines; 2) DDC does not stimulate responses in the HPA axis in the absence of B; and, 3) facilitation of HPA responses to acute stres s depends on increased steady-state B signals. Facilitated responses a re probably not mediated by catecholamines. The consequence of facilit ation is that under conditions of chronic stress and elevated B concen trations, as in depression or anorexia nervosa in man, or adjuvent-ind uced arthritis in rats, the HPA axis is continually responsive to new stimuli.