Corticotropin releasing factor (CRF) modulates fear-induced alterations in sleep in mice.
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 microl, n=9), CRF (0.4 microg, n=8), or AST (1.0 microg, 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.
Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501, USA.
Linghui
L
Yang
Xiangdong
X
Tang
Laurie L
LL
Wellman
Xianling
X
Liu
Larry D
LD
Sanford
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002404:Catheterization; D003214:Conditioning, Classical; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003624:Darkness; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004597:Electroshock; D004777:Environment; D005239:Fear; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D010446:Peptide Fragments / Q000008:administration & dosage; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology
D010446:Peptide Fragments; C104416:astressin; D003346:Corticotropin-Releasing Hormone