Corticotropin releasing factor (CRF) modulates fear-induced alterations in sleep in mice

• Published in: Brain research 2009-06, Vol.1276, p.112-122
• Main Authors: Yang, Linghui, Tang, Xiangdong, Wellman, Laurie L, Liu, Xianling, Sanford, Larry D
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; Biological and medical sciences; Brain - drug effects; Brain - physiology; Catheterization; Conditioning, Classical; Corticotropin releasing factor; Corticotropin-Releasing Hormone - administration & dosage; Corticotropin-Releasing Hormone - antagonists & inhibitors; Corticotropin-Releasing Hormone - metabolism; Darkness; Electrodes, Implanted; Electroencephalography; Electroshock; Environment; Fear; Fundamental and applied biological sciences. Psychology; Male; Mice; Mice, Inbred BALB C; Microinjections; Neurology; Peptide Fragments - administration & dosage; Sleep; Sleep - drug effects; Sleep - physiology; Sleep, REM - drug effects; Sleep, REM - physiology; Sleep. Vigilance; Stress; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.04.017

Abstract Contextual fear significantly reduces rapid eye movement sleep (REM) during post-exposure sleep in mice and rats. Corticotropin releasing factor (CRF) plays a major role in CNS responses to stressors. We examined the influence of CRF and astressin (AST), a non-specific CRF antagonist, on sleep after contextual fear in BALB/c mice. Male mice were implanted with transmitters for recording sleep via telemetry and with a guide cannula aimed into the lateral ventricle. Recordings for vehicle and handling control were obtained after ICV microinjection of saline (SAL) followed by exposure to a novel chamber. Afterwards, the mice were subjected to shock training (20 trials, 0.5 mA, 0.5 s duration) for 2 sessions. After training, separate groups of mice received ICV microinjections of SAL (0.2 μl, n = 9), CRF (0.4 μg, n = 8), or AST (1.0 μg, n = 8) prior to exposure to the shock context alone. Sleep was then recorded for 20 h (8-hour light and 12-hour dark period). Compared to handling control, contextual fear significantly decreased REM during the 8-h light period in mice receiving SAL and in mice receiving CRF, but not in the mice receiving AST. Mice receiving CRF exhibited reductions in REM during the 12-h dark period after contextual fear, whereas mice receiving SAL or AST did not. CRF also reduced non-REM (NREM) delta (slow wave) amplitude in the EEG. Only mice receiving SAL prior to contextual fear exhibited significant reductions in NREM and total sleep. These findings demonstrate a role for the central CRF system in regulating alterations in sleep induced by contextual fear.