Evidence for Central Norepinephrine-Mediated Inhibition of ACTH Secretion in the Rat

At 8 h after injection of guanethidine, 1 mg/kg, into the third ventricle of the brain in male rats, plasma corticosterone was 38.8±3.2 µg/100 ml and hypothalamic norepinephrine (NE) and dopamine (DA) were l.08±0.l0 and 0.27±0.06 µg/g, respectively. After intraperitoneal injection of guanethidine, 30 mg/kg, plasma corticosterone was 4.7 ± 1.1 and hypothalamic NE and DA were 1.86 ± 0.09 and 0.37 ± 0.08. Since guanethidine does not cross the blood-brain barrier, these observations support the hypothesis that adrenergic inhibition of ACTH secretion is mediated by adrenergic neurons in the central nervous system. Following specific depletion of NE by FLA-63, an inhibitor of dopamine-β-oxidase, plasma corticosterone was 56.4 ± 6.2. Hypothalamic NE content was decreased 50% while DA content was unchanged. This suggests that the adrenergic inhibition is mediated by norepinephrine rather than dopamine.