Medullary neurones regulate hypothalamic corticotropin-releasing factor cell responses to an emotional stressor

• Published in: Neuroscience Vol. 105; no. 3; pp. 707 - 719
• Main Authors: Dayas, C.V, Buller, K.M, Day, T.A
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.01.2001; Elsevier
• Subjects: Adrenocorticotropic Hormone - metabolism; amygdala; Amygdala - cytology; Amygdala - metabolism; Animals; Biological and medical sciences; Catecholamines - metabolism; Cell Count; Corticotropin-Releasing Hormone - metabolism; Denervation; Fundamental and applied biological sciences. Psychology; General aspects. Hormone interactions. Hormone actions on several organ systems. Adaptive reactions; Gold Colloid - pharmacokinetics; hypothalamic–pituitary–adrenal axis; Hypothalamo-Hypophyseal System - cytology; Hypothalamo-Hypophyseal System - metabolism; Immunohistochemistry; Male; Medulla Oblongata - cytology; Medulla Oblongata - metabolism; Nerve Degeneration - chemically induced; Neural Pathways - cytology; Neural Pathways - metabolism; Neurons - cytology; Neurons - metabolism; noradrenergic cells; nucleus of the solitary tract; Oxidopamine - pharmacology; Paraventricular Hypothalamic Nucleus - cytology; Paraventricular Hypothalamic Nucleus - metabolism; Presynaptic Terminals - drug effects; Presynaptic Terminals - metabolism; Proto-Oncogene Proteins c-fos - metabolism; Rats; Rats, Wistar; restraint; Restraint, Physical - adverse effects; Solitary Nucleus - cytology; Solitary Nucleus - metabolism; Stress, Physiological - metabolism; Stress, Physiological - physiopathology; synaptic pathway; ventrolateral medulla; Vertebrates: endocrinology; Wheat Germ Agglutinins - pharmacokinetics; LHS, left-hand side; amygdala; RHS, right-hand side; hypothalamic–pituitary–adrenal axis; DBH, dopamine β-hydroxylase; CTb, cholera toxin subunit b; MeA, medial amygdala; pm, posterior magnocellular; TH, tyrosine hydroxylase; ANOVA, analysis of variance; ventrolateral medulla; CRF, corticotropin-releasing factor; SON, supraoptic nucleus; noradrenergic cells; nucleus of the solitary tract; PVN, paraventricular nucleus; VLM, ventrolateral medulla; ACTH, adrenocorticotropin hormone; CA, catecholamine; mp, medial parvocellular; restraint; PNMT, phenyl- N-methyl transferase; 6-OHDA, 6-hydroxydopamine; NTS, nucleus of the solitary tract; CeA, central amygdala; WGA-Au, wheat germ agglutinin-conjugated gold; HPA, hypothalamic–pituitary–adrenal; OT, oxytocin; Affect affectivity; Amygdala; Rat; Hypothalamohypophysoadrenal axis; Noradrenergic neuron; Rodentia; Central nervous system; Corticotropin releasing factor; Emotion emotionality; Hypothalamus; Stress; Hypothalamic hormone; Solitary nucleus; Vertebrata; Mammalia; Medulla oblongata; Hormone releasing factor; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(01)00213-5

Hypothalamic–pituitary–adrenal axis activation is a hallmark of the stress response. In the case of physical stressors, there is considerable evidence that medullary catecholamine neurones are critical to the activation of the paraventricular nucleus corticotropin-releasing factor cells that constitute the apex of the hypothalamic–pituitary–adrenal axis. In contrast, it has been thought that hypothalamic–pituitary–adrenal axis responses to emotional stressors do not involve brainstem neurones. To investigate this issue we have mapped patterns of restraint-induced neuronal c- fos expression in intact animals and in animals prepared with either paraventricular nucleus-directed injections of a retrograde tracer, lesions of paraventricular nucleus catecholamine terminals, or lesions of the medulla corresponding to the A1 or A2 noradrenergic cell groups. Restraint-induced patterns of neuronal activation within the medulla of intact animals were very similar to those previously reported in response to physical stressors, including the fact that most stressor-responsive, paraventricular nucleus-projecting cells were certainly catecholaminergic and probably noradrenergic. Despite this, the destruction of paraventricular nucleus catecholamine terminals with 6-hydroxydopamine did not alter corticotropin-releasing factor cell responses to restraint. However, animals with ibotenic acid lesions encompassing either the A1 or A2 noradrenergic cell groups displayed significantly suppressed corticotropin-releasing factor cell responses to restraint. Notably, these medullary lesions also suppressed neuronal responses in the medial amygdala, an area that is now considered critical to hypothalamic–pituitary–adrenal axis responses to emotional stressors and that is also known to display a significant increase in noradrenaline turnover during restraint. We conclude that medullary neurones influence corticotropin-releasing factor cell responses to emotional stressors via a multisynaptic pathway that may involve a noradrenergic input to the medial amygdala. These results overturn the idea that hypothalamic–pituitary–adrenal axis response to emotional stressors can occur independently of the brainstem.