title: A rodent model of traumatic stress induces lasting sleep and quantitative electroencephalographic disturbances.
abstract: Hyperarousal and sleep disturbances are common, debilitating symptoms of post-traumatic stress disorder (PTSD). PTSD patients also exhibit abnormalities in quantitative electroencephalography (qEEG) power spectra during wake as well as rapid eye movement (REM) and non-REM (NREM) sleep. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for PTSD, provide modest remediation of the hyperarousal symptoms in PTSD patients, but have little to no effect on the sleep-wake architecture deficits. Development of novel therapeutics for these sleep-wake architecture deficits is limited by a lack of relevant animal models. Thus, the present study investigated whether single prolonged stress (SPS), a rodent model of traumatic stress, induces PTSD-like sleep-wake and qEEG spectral power abnormalities that correlate with changes in central serotonin (5-HT) and neuropeptide Y (NPY) signaling in rats. Rats were implanted with telemetric recording devices to continuously measure EEG before and after SPS treatment. A second cohort of rats was used to measure SPS-induced changes in plasma corticosterone, 5-HT utilization, and NPY expression in brain regions that comprise the neural fear circuitry. SPS caused sustained dysregulation of NREM and REM sleep, accompanied by state-dependent alterations in qEEG power spectra indicative of cortical hyperarousal. These changes corresponded with acute induction of the corticosterone receptor co-chaperone FK506-binding protein 51 and delayed reductions in 5-HT utilization and NPY expression in the amygdala. SPS represents a preclinical model of PTSD-related sleep-wake and qEEG disturbances with underlying alterations in neurotransmitter systems known to modulate both sleep-wake architecture and the neural fear circuitry.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Nedelcovych
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gould
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhan
authors.forename: Michael
authors.initials: M
authors.lastname: Bubser
authors.forename: Xuewen
authors.initials: X
authors.lastname: Gong
authors.forename: Michael
authors.initials: M
authors.lastname: Grannan
authors.forename: Analisa T
authors.initials: AT
authors.lastname: Thompson
authors.affiliation: ∥Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Magnus
authors.initials: M
authors.lastname: Ivarsson
authors.affiliation: §Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37232, United States.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: P Jeffrey
authors.initials: PJ
authors.lastname: Conn
authors.forename: Carrie K
authors.initials: CK
authors.lastname: Jones
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D004569:Electroencephalography; D004576:Electromyography; D005583:Fourier Analysis; D007211:Indoles / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000235:genetics / Q000378:metabolism; D012893:Sleep Wake Disorders / Q000175:diagnosis / Q000209:etiology*; D013313:Stress Disorders, Post-Traumatic / Q000097:blood / Q000150:complications*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D007211:Indoles; D009478:Neuropeptide Y; D012333:RNA, Messenger; D012701:Serotonin; C024139:indole-3-lactic acid; D022021:Tacrolimus Binding Proteins; D003345:Corticosterone
keywords: FKBP5; Single prolonged stress (SPS); electroencephalography (EEG); neuropeptide Y (NPY); post-traumatic stress disorder (PTSD); serotonin (5-HT)