Post-exposure sleep deprivation facilitates correctly timed interactions between glucocorticoid and adrenergic systems, which attenuate traumatic stress responses

Neuropsychopharmacology. 2012 Oct;37(11):2388-404. doi: 10.1038/npp.2012.94. Epub 2012 Jun 20.

Abstract

Reliable evidence supports the role of sleep in learning and memory processes. In rodents, sleep deprivation (SD) negatively affects consolidation of hippocampus-dependent memories. As memory is integral to post-traumatic stress symptoms, the effects of post-exposure SD on various aspect of the response to stress in a controlled, prospective animal model of post-traumatic stress disorder (PTSD) were evaluated. Rats were deprived of sleep for 6 h throughout the first resting phase after predator scent stress exposure. Behaviors in the elevated plus-maze and acoustic startle response tests were assessed 7 days later, and served for classification into behavioral response groups. Freezing response to a trauma reminder was assessed on day 8. Urine samples were collected daily for corticosterone levels, and heart rate (HR) was also measured. Finally, the impact of manipulating the hypothalamus-pituitary-adrenal axis and adrenergic activity before SD was assessed. Mifepristone (MIFE) and epinephrine (EPI) were administered systemically 10-min post-stress exposure and behavioral responses and response to trauma reminder were measured on days 7-8. Hippocampal expression of glucocorticoid receptors (GRs) and morphological assessment of arborization and dendritic spines were subsequently evaluated. Post-exposure SD effectively ameliorated long-term, stress-induced, PTSD-like behavioral disruptions, reduced trauma reminder freezing responses, and decreased hippocampal expression of GR compared with exposed-untreated controls. Although urine corticosterone levels were significantly elevated 1 h after SD and the HR was attenuated, antagonizing GRs with MIFE or stimulation of adrenergic activity with EPI effectively abolished the effect of SD. MIFE- and EPI-treated animals clearly demonstrated significantly lower total dendritic length, fewer branches and lower spine density along dentate gyrus dendrites with increased levels of GR expression 8 days after exposure, as compared with exposed-SD animals. Intentional prevention of sleep in the early aftermath of stress exposure may well be beneficial in attenuating traumatic stress-related sequelae. Post-exposure SD may disrupt the consolidation of aversive or fearful memories by facilitating correctly timed interactions between glucocorticoid and adrenergic systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / adverse effects
  • Adrenergic Agonists / pharmacology
  • Adrenergic Agonists / therapeutic use*
  • Analysis of Variance
  • Animals
  • Corticosterone / urine
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Dendrites / ultrastructure
  • Disease Models, Animal
  • Electrocardiography
  • Epinephrine / therapeutic use*
  • Freezing Reaction, Cataleptic / drug effects
  • Freezing Reaction, Cataleptic / physiology
  • Gene Expression Regulation / drug effects
  • Heart Rate / drug effects
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Hippocampus / ultrastructure
  • Hormone Antagonists / pharmacology
  • Hormone Antagonists / therapeutic use*
  • Male
  • Maze Learning / drug effects
  • Mifepristone / pharmacology
  • Mifepristone / therapeutic use*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Glucocorticoid / metabolism
  • Reflex, Startle / drug effects
  • Reflex, Startle / physiology
  • Silver Staining
  • Sleep Deprivation / physiopathology*
  • Stress Disorders, Post-Traumatic / physiopathology
  • Stress Disorders, Post-Traumatic / prevention & control*
  • Telemetry
  • Time Factors

Substances

  • Adrenergic Agonists
  • Hormone Antagonists
  • Receptors, Glucocorticoid
  • Mifepristone
  • Corticosterone
  • Epinephrine