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.