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Serotonergic involvement in stress-induced ACTH release
H Jørgensen1, U Knigge, A Kjaer
1Department of Medical Physiology, The Panum Institute 12.3, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark. hsj@mfi.ku.dk
Brain Research
|November 7, 1998
Summary
Serotonin (5-HT) and specific 5-HT receptors mediate stress-induced ACTH secretion in rats. Serotonergic neurons in the raphe nuclei and hypothalamus are key to this stress response.
Area of Science:
- Neuroendocrinology
- Neuropharmacology
- Stress Physiology
Background:
- The hypothalamic-pituitary-adrenal (HPA) axis is a primary stress response system.
- Serotonin (5-HT) is implicated in regulating the HPA axis, but its specific role in stress-induced ACTH secretion is complex.
- Understanding the involvement of different 5-HT receptor subtypes is crucial for elucidating stress pathways.
Purpose of the Study:
- To investigate the role of serotonin (5-HT) and its receptors in mediating adrenocorticotropic hormone (ACTH) secretion under various stress conditions in rats.
- To identify specific 5-HT receptor subtypes involved in the stress response.
- To explore the activation of serotonergic neurons during stress.
Main Methods:
- Adult male rats were subjected to different stressors (restraint, ether, cold swim, endotoxin).
- 5-HT neuron lesions were induced using 5,7-dihydroxytryptamine.
- Rats were pretreated with various 5-HT receptor antagonists (e.g., WAY 100635, methysergide, ketanserin, LY 53857, ondansetrone, tropisetrone).
- Plasma ACTH levels were measured.
- 5-HT and 5-HIAA levels in the raphe nuclei were analyzed.
Main Results:
- All stressors significantly increased plasma ACTH.
- 5-HT neuron lesions reduced restraint stress-induced ACTH by 50%.
- Restraint stress increased 5-HT and 5-HIAA in the raphe nuclei.
- 5-HT1A, 5-HT2A, and 5-HT2C receptor antagonists partially or fully inhibited ACTH secretion in response to specific stressors.
- 5-HT3 receptor antagonism had no effect, while 5-HT4 involvement was suggested.
- Swim stress-induced ACTH was not affected by antagonists.
Conclusions:
- Serotonin (5-HT) plays a significant role in mediating stress-induced ACTH secretion.
- 5-HT1A, 5-HT2A, and 5-HT2C receptors are involved in this response, while 5-HT3 receptors are not.
- Serotonergic neurons in the raphe nuclei are activated by restraint stress.
- These serotonergic neurons and hypothalamic neurons are critical for mediating restraint stress-induced ACTH release.