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: Michael T Nedelcovych, Robert W Gould, Xiaoyan Zhan, Michael Bubser, Xuewen Gong, Michael Grannan, Analisa T Thompson, Magnus Ivarsson, Craig W Lindsley, P Jeffrey Conn, Carrie K Jones
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 6 Issue 3 Pg. 485-93 (Mar 18 2015) ISSN: 1948-7193 [Electronic] United States
• PMID: 25581551 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Indoles
• Neuropeptide Y
• RNA, Messenger
• Serotonin
• indole-3-lactic acid
• Tacrolimus Binding Proteins
• Corticosterone

Topics

• Analysis of Variance
• Animals
• Brain Waves (drug effects, physiology)
• Corticosterone (blood)
• Disease Models, Animal
• Electroencephalography
• Electromyography
• Fourier Analysis
• Indoles (metabolism)
• Male
• Neuropeptide Y (genetics, metabolism)
• RNA, Messenger
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Serotonin (genetics, metabolism)
• Sleep Wake Disorders (diagnosis, etiology)
• Stress Disorders, Post-Traumatic (blood, complications)
• Tacrolimus Binding Proteins (metabolism)
• Time Factors