Locus Coeruleus Noradrenergic Modulation of Diurnal Corticosterone, Stress Reactivity, and Cardiovascular Homeostasis in Male Rats

Neuroendocrinology. 2022;112(8):763-776. doi: 10.1159/000520192. Epub 2021 Oct 14.

Abstract

Introduction: Activation of the locus coeruleus-noradrenergic (LC-NA) system during awakening is associated with an increase in plasma corticosterone and cardiovascular tone. These studies evaluate the role of the LC in this corticosterone and cardiovascular response.

Methods: Male rats, on day 0, were treated intraperitoneally with either DSP4 (50 mg/kg body weight) (DSP), an LC-NA specific neurotoxin, or normal saline (SAL). On day 10, animals were surgically prepared with jugular vein (hypothalamic-pituitary-adrenal [HPA] axis) or carotid artery (hemodynamics) catheters and experiments performed on day 14. HPA axis activity, diurnally (circadian) and after stress (transient hemorrhage [14 mL/kg body weight] or air puff-startle), and basal and post-hemorrhage hemodynamics were evaluated. On day 16, brain regions from a subset of rats were dissected for norepinephrine and corticotropin-releasing factor (CRF) assay.

Results: In DSP rats compared to SAL rats, (1) regional brain norepinephrine was decreased, but there was no change in median eminence or olfactory bulb CRF content; (2) during HPA axis acrophase, the plasma corticosterone response was blunted; (3) after hemorrhage and air puff-startle, the plasma adrenocorticotropic hormone response was attenuated, whereas the corticosterone response was dependent on stressor category; (4) under basal conditions, hemodynamic measures exhibited altered blood flow dynamics and systemic vasodilation; and (5) after hemorrhage, hemodynamics exhibited asynchronous responses.

Conclusion: LC-NA modulation of diurnal and stress-induced HPA axis reactivity occurs via distinct neurocircuits. The integrity of the LC-NA system is important to maintain blood flow dynamics. The importance of increases in plasma corticosterone at acrophase to maintain short- and long-term cardiovascular homeostasis is discussed.

Keywords: Cardiac output; Corticolimbic circuitry; Liljestrand and Zander equation; Sympathoadrenal; Vascular tone.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenocorticotropic Hormone
  • Animals
  • Body Weight
  • Corticosterone*
  • Corticotropin-Releasing Hormone / metabolism
  • Homeostasis
  • Hypothalamo-Hypophyseal System / metabolism
  • Locus Coeruleus / metabolism
  • Male
  • Norepinephrine
  • Pituitary-Adrenal System* / metabolism
  • Rats

Substances

  • Adrenocorticotropic Hormone
  • Corticotropin-Releasing Hormone
  • Corticosterone
  • Norepinephrine