PMID- 12191624
OWN - NLM
STAT- MEDLINE
DCOM- 20021029
LR  - 20190922
IS  - 0022-3956 (Print)
IS  - 0022-3956 (Linking)
VI  - 36
IP  - 4
DP  - 2002 Jul-Aug
TI  - The CRH1 receptor antagonist R121919 attenuates stress-elicited sleep 
      disturbances in rats, particularly in those with high innate anxiety.
PG  - 197-208
AB  - Excessive corticotropin-releasing hormone (CRH) secretion in limbic and 
      prefrontal brain areas has been postulated to underly stress-related clinical 
      conditions. Studies in mice with deleted or pharmacologically compromised CRH 
      type 1 receptors (CRH-R1) point to a key role of the CRH/CRH-R1 signaling cascade 
      as a potential drug target. Therefore, we compared the effect of a selective high 
      affinity CRH-R1 antagonist (R121919) on sleep-wake behavior in two rat lines 
      selectively bred for either high or low innate anxiety. We found that the 
      subcutaneous injection of the solvent of R121919, a citrate buffer solution, 
      transiently increased circulating levels of the stress hormones ACTH and 
      corticosterone and reduced sleep, especially in high-anxiety animals. When 
      R121919 was added to the solvent, hormone levels and sleep patterns returned to 
      baseline and were indistinguishable between the rat lines. This finding is in 
      accord with previous observations from a clinical trial in depressed patients and 
      studies in rats with high innate anxiety that suggested major effects of CRH-R1 
      antagonism in the presence of a pathological (i.e. CRH hypersecretion) condition 
      only.
CI  - Copyright 2002 Elsevier Science Ltd.
FAU - Lancel, Marike
AU  - Lancel M
AD  - Max Planck Institute of Psychiatry, Section Neurophysiology, Kraepelinstr. 2-10, 
      D-80804, Munich, Germany.
FAU - Muller-Preuss, Peter
AU  - Muller-Preuss P
FAU - Wigger, Alexandra
AU  - Wigger A
FAU - Landgraf, Rainer
AU  - Landgraf R
FAU - Holsboer, Florian
AU  - Holsboer F
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Psychiatr Res
JT  - Journal of psychiatric research
JID - 0376331
RN  - 0 (Pyrimidines)
RN  - 0 (R 121919)
RN  - 0 (Receptors, Corticotropin-Releasing Hormone)
RN  - 5CLY6W2H1M (CRF receptor type 1)
RN  - 9002-60-2 (Adrenocorticotropic Hormone)
RN  - W980KJ009P (Corticosterone)
SB  - IM
MH  - Adrenocorticotropic Hormone/blood
MH  - Animals
MH  - Arousal/*drug effects
MH  - Corticosterone/blood
MH  - Hypothalamo-Hypophyseal System/drug effects
MH  - Limbic System/drug effects
MH  - Male
MH  - Pituitary-Adrenal System/drug effects
MH  - Prefrontal Cortex/drug effects
MH  - Pyrimidines/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Corticotropin-Releasing Hormone/*antagonists & inhibitors
MH  - Sleep Stages/*drug effects
MH  - Wakefulness/drug effects
EDAT- 2002/08/23 10:00
MHDA- 2002/10/31 04:00
CRDT- 2002/08/23 10:00
PHST- 2002/08/23 10:00 [pubmed]
PHST- 2002/10/31 04:00 [medline]
PHST- 2002/08/23 10:00 [entrez]
AID - S0022395602000092 [pii]
AID - 10.1016/s0022-3956(02)00009-2 [doi]
PST - ppublish
SO  - J Psychiatr Res. 2002 Jul-Aug;36(4):197-208. doi: 10.1016/s0022-3956(02)00009-2.