Hypothalamic Monoamine Control of Stress-Induced Adrenocorticotropin Release in the Rat*

Abstract

Despite evidence that ACTH release after stress is under excitatory hypothalamic control, a stimulatory role for any of the monoamine neurotransmitters is yet to be clearly demonstrated. Computerized gas chromatography/mass spectrometry was used to assess the neuronal activities of hypothalamic dopamine, norephinephrine (NE) and serotonin (5-HT) in rats after stress-induced ACTH release. Medial basal hypothalamic NE neuronal activity as assessed by the ratio of 3,4-dihydroxyphenylethyleneglycol (DHPG) to NE. (DHPG/NE) was elevated (P < 0.0005) within 2 min after a 3-min cold water swim stress. Ether stress also caused a marked elevation in NE activity (P < 0.0025). A highly significant positive correlation between the ratio of hypothalamic DHPG/NE and serum corticosterone was found over a large population of normal and stressed rats. Consistent with this relationship between hypothalamic NE neuronal activity and ACTH release being a causal one were the findings that adrenalectomized rats exhibited markedly elevated hypothalamic DHPG/NE ratio and serum ACTH (both P < 0.0005) together with serum corticosterone levels reduced to about 3% of control levels (P < 0.0005), and the administration to rats of the .alpha.-blocker yohimbine or the antianxiety agent diazepam resulted in significant changes in hypothalamic NE activity, together with parallel changes in ACTH secretion. In hypothyroid rats, which have elevated hypothalamic 5-HT activity, and in normal gentled rats, stress caused a significant reduction in hypothalamic 5-HT activity. High hypothalamic activity of dopamin or 5-HT in hypothyroid rats did not significantly affect basal ACTH levels nor prevent the responses to either cold water swim or ether stress, and both stresses resulted in elevated hypothalamic DHPG/NE, serum ACTH and serum corticosterone (all P < 0.005) in these animals. NE is an excitatory hypothalamic monoamine for ACTH release in stress and hypothalamic 5-HT activity is reduced after stress.