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Maraviroc, a CCR5 chemokine blocker, enhanced corticosterone release in a post-traumatic stress disorder model in rats: the effects of chronic stress and fear on the hippocampal CCR5/RANTES axis.
* 1 , 2 , 3 , 4
1  UCM (Universidad Complutense de Madrid), Dpto. Farmacología, Farmacognosia y Botánica (UCM), IUIN, Spain
2  Universidad de La Salle (Colombia)
3  Psychobiology Dept. UNED (Madrid, Spain)
4  Harvard Medical School. MGH (Boston, USA)
Academic Editor: Keehoon Lee

Abstract:

Contextual fear conditioning (CFC) is a stress behavioural paradigm that resembles many characteristics of post-traumatic stress disorder (PSTD). It is well documented that PTSD is associated with inflammation; however, there is limited information on how inflammation contributes to the progresison and development of PTSD. Because PTSD is difficult to treat, the understanding of the inflammatory mediators involved in this pathology could favour better interventions against its resilience. In fact, higher IL-6 levels in CFC of susceptible rats prior to trauma can increase the PTSD susceptibility in rats. In this study, we have evaluated whether PSTD fear learning may increase CCR5/RANTES levels by chronic stress restraint (21 days of restraint, 6 h/day) and/or fear learning; these chemokines (CCR5/RANTES) were quantified by ELISA in synaptosomes from the hippocampus and rat prefrontal cortex. This PSTD model increases CCR5/RANTES at 24 h post-training, but chronic stress did not affect these chemokine levels. We also evaluted whether the CCR5 blockade by maraviros (a CCR5 chemokine blocker) before CFC training is able to prevent fear behavior and also normalize RANTES, IL-6, or cortisol release as compared to CFC-trained rats. Maraviroc (a CCR5 chemokine blocker) enhanced corticosterone release in this PSTD paradigm. The CCR5 blockade by mararviroc enhanced corticosterone release, which suggests a neurohormonal regulation of the CCR5 chemokine receptor in the rat hippocampus.

Keywords: beta chemokines, PSTD, stress; neuroinflammation; neuropsychiatry

 
 
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