Abstract | RATIONALE: The selective CRF1 ( corticotropin releasing factor type 1) receptor antagonist SSR125543 has been previously shown to attenuate the long-term cognitive deficit produced by traumatic stress exposure. Memory disturbances described in post-traumatic stress disorder ( PTSD) patients are believed to be associated with changes in neuronal activity, in particular at the level of the hippocampus. OBJECTIVES: METHODS: Mice received two unavoidable electric foot-shocks. Then, 1 or 16 days after stress, they were tested for their memory performance using the object recognition test. Neuronal excitability was recorded during the third week post-stress in the CA1 area of the hippocampus. Drugs were administered from day 1 post-stress to the day preceding the electrophysiological study. RESULTS: Application of electric shocks produced cognitive impairment 16, but not 1 day after stress, an effect which was associated with a decrease in hippocampal neuronal excitability. Both stress-induced effects were prevented by repeated administration of SSR125543, paroxetine and D- cycloserine. CONCLUSIONS: These findings confirm that the CRF1 receptor antagonist SSR125543 is able to attenuate the behavioral effects of traumatic stress exposure and indicate that these effects are associated with a normalization of hippocampal neuronal excitability impaired by stress.
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Authors | J Philbert, C Belzung, G Griebel |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 228
Issue 1
Pg. 97-107
(Jul 2013)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 23407783
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Hydrocarbons, Halogenated
- Receptors, Corticotropin-Releasing Hormone
- SSR125543
- Serotonin Uptake Inhibitors
- Thiazines
- Paroxetine
- CRF receptor type 1
- Cycloserine
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Topics |
- Animals
- Behavior, Animal
(drug effects)
- Cognition Disorders
(drug therapy, etiology)
- Cycloserine
(pharmacology)
- Electroshock
- Hippocampus
(drug effects, pathology)
- Hydrocarbons, Halogenated
(pharmacology)
- Male
- Mice
- Paroxetine
(pharmacology)
- Receptors, Corticotropin-Releasing Hormone
(antagonists & inhibitors)
- Selective Serotonin Reuptake Inhibitors
(pharmacology)
- Stress, Psychological
(complications, drug therapy)
- Thiazines
(pharmacology)
- Time Factors
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