PMID- 20394311
OWN - NLM
STAT- MEDLINE
DCOM- 20100507
LR  - 20211020
IS  - 0161-8105 (Print)
IS  - 1550-9109 (Electronic)
IS  - 0161-8105 (Linking)
VI  - 33
IP  - 4
DP  - 2010 Apr
TI  - Central deficiency of corticotropin-releasing hormone receptor type 1 (CRH-R1) 
      abolishes effects of CRH on NREM but not on REM sleep in mice.
PG  - 427-36
AB  - STUDY OBJECTIVES: Corticotropin-releasing hormone (CRH) is the major activator of 
      the hypothalamic-pituitary-adrenocortical (HPA) system and orchestrates the 
      neuroendocrine, autonomous as well as behavioral responses to stress. Many 
      studies suggest an influence of CRH on sleep-wake regulation even in the absence 
      of stressors. However, none of these studies yet clearly distinguished between 
      central and peripheral effects of CRH. Therefore, we investigated in CNS-specific 
      CRH receptor type 1 deficient mice whether centrally administered CRH could 
      induce its sleep-wake modulatory effects without peripheral induction of HPA 
      activity. DESIGN: Male mice (C57BL/6J, CNS-specific CRH-R1 knockout [CKO] mice 
      and their control littermates [CL]) were intracerebroventricularily (i.c.v.) 
      injected with vehicle or 3 different doses of CRH shortly before the beginning of 
      the light period. Electroencephalogram (EEG) and electromyogram (EMG) were 
      monitored to compare the effects of CRH on vigilance states with or without 
      presence of central CRH-R1. To quantify HPA-axis reactivity to CRH injections in 
      CKO and CL animals, blood samples were analyzed to determine plasma 
      corticosterone concentrations. RESULTS: I.c.v. injections of CRH promoted 
      wakefulness while decreasing NREMS in C57BL/6J and CRH-R1 CL animals, whereas 
      such changes were not exerted in CKO mice. However, REMS suppression after CRH 
      application persisted in all animals. I.c.v. injected CRH increased plasma 
      corticosterone levels in both CL and CKO mice. CONCLUSIONS: The results 
      demonstrated that CRH has a major impact on wake and NREMS regulation which is 
      predominantly mediated through central CRH-R1. Peripheral actions of CRH, i.e., 
      elevated HPA activity, may interfere with its central effects on REMS but not on 
      NREMS suppression.
FAU - Romanowski, Christoph P N
AU  - Romanowski CP
AD  - Max Planck Institute of Psychiatry, Munich, Germany.
FAU - Fenzl, Thomas
AU  - Fenzl T
FAU - Flachskamm, Cornelia
AU  - Flachskamm C
FAU - Wurst, Wolfgang
AU  - Wurst W
FAU - Holsboer, Florian
AU  - Holsboer F
FAU - Deussing, Jan M
AU  - Deussing JM
FAU - Kimura, Mayumi
AU  - Kimura M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Sleep
JT  - Sleep
JID - 7809084
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Animals
MH  - Arousal/drug effects
MH  - Corticosterone/blood
MH  - Corticotropin-Releasing Hormone/*administration & dosage/blood
MH  - Dose-Response Relationship, Drug
MH  - Electroencephalography/methods
MH  - Electromyography/methods
MH  - Hypothalamo-Hypophyseal System/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Pituitary-Adrenal System/drug effects
MH  - Receptors, Corticotropin-Releasing Hormone/blood/*deficiency
MH  - Sleep Stages/drug effects
MH  - Sleep, REM/*drug effects
MH  - Time Factors
MH  - Wakefulness/drug effects
PMC - PMC2849781
EDAT- 2010/04/17 06:00
MHDA- 2010/05/08 06:00
PMCR- 2010/10/01
CRDT- 2010/04/17 06:00
PHST- 2010/04/17 06:00 [entrez]
PHST- 2010/04/17 06:00 [pubmed]
PHST- 2010/05/08 06:00 [medline]
PHST- 2010/10/01 00:00 [pmc-release]
AID - 10.1093/sleep/33.4.427 [doi]
PST - ppublish
SO  - Sleep. 2010 Apr;33(4):427-36. doi: 10.1093/sleep/33.4.427.