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

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 IP with either DSP4 (50 mg/ kg body weight) (DSP), a 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 airpuff-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 airpuff-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.