Norepinephrine release in medial amygdala facilitates activation of the hypothalamic-pituitary-adrenal axis in response to acute immobilisation stress

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Activation of the brain noradrenergic system during stress plays an important integrative function in coping and stress adaptation by facilitating transmission in many brain regions involved in regulating behavioural and physiological components of the stress response. The medial amygdala (MeA) has been implicated in modulation of stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, and MeA is a target of innervation from brainstem noradrenergic neurones. However, it is not known whether, and to what extent, activation of the ascending noradrenergic innervation of MeA might modulate stress-induced adrenocorticotropic hormone (ACTH) secretion. In the first experiment in this study, we measured extracellular norepinephrine (NE) levels in MeA using in vivo microdialysis. The concentration of NE in dialysate samples collected in MeA was elevated by more than three-fold over baseline in response to acute immobilisation stress, providing evidence of a possible modulatory role for NE in the MeA during stress. This potential role was then assessed in the second experiment by measuring changes in the elevation of plasma ACTH concentration induced by acute immobilisation stress immediately following bilateral microinjections of α1- or β-adrenergic receptor antagonists directly into MeA. Compared to vehicle-injected controls, the α1-receptor antagonist benoxathian dose-dependently and significantly attenuated the ACTH response to acute stress, whereas combined β12-receptor blockade in MeA had only a modest effect. These results indicate that MeA does play a role in the stress response, and support the hypothesis that stress-induced activation of NE release in MeA, acting primarily through α1 receptors, facilitates activation of the HPA axis in response to acute stress.

Original languageEnglish (US)
Pages (from-to)22-28
Number of pages7
JournalJournal of Neuroendocrinology
Issue number1
StatePublished - Jan 2005


  • Hypothalamic-pituitary-adrenal axis
  • Medial amygdala
  • Norepinephrine
  • Stress
  • α-adrenergic receptors

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Endocrinology
  • Cellular and Molecular Neuroscience
  • Endocrinology, Diabetes and Metabolism


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