TITLE

The CRF receptor antagonist SSR125543 prevents stress-induced cognitive deficit associated with hippocampal dysfunction: Comparison with paroxetine and d-cycloserine

AUTHOR(S)
Philbert, J.; Belzung, C.; Griebel, G.
PUB. DATE
July 2013
SOURCE
Psychopharmacology;Jul2013, Vol. 228 Issue 1, p97
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Rationale: The selective CRF (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: The present study aims at investigating whether the effects of SSR125543 (10 mg/kg/day for 2 weeks) on cognitive impairment induced by traumatic stress exposure are associated with changes in hippocampal excitability. Effects of SSR125543 were compared to those of the 5-HT reuptake inhibitor, paroxetine (10 mg/kg/day), and the partial N-methyl- d-aspartate (NMDA) receptor agonist, d-cycloserine (10 mg/kg/day), two compounds which have demonstrated clinical efficacy against PTSD. 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 CRF 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.
ACCESSION #
88060298

 

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