β-endorphin degradation and the individual reactivity to traumatic stress

Alexandra Kavushansky, Milli Kritman, Mouna Maroun, Ehud Klein, Gal Richter-Levin, Koon Sea Hui, Dorit Ben-Shachar

Research output: Contribution to journalArticlepeer-review

Abstract

Reactivity to traumatic stress varies between individuals and only a minority of those exposed to trauma develops stress-induced psychopathologies. Currently extensive effort is made to unravel the specific mechanisms predisposing to vulnerability vs. resilience to stress. We investigated in rats the role of β-endorphin metabolism in vulnerability to acute traumatic stress. Responders (showing extreme anxiety; n=7) and resilient non-responders (not differing from the non-stressed individuals; n=8) to traumatic foot-shock stress were compared for their blood levels of stress hormones as well as brain levels and activity of two opioid-degrading enzymes. β-endorphin is a substrate to insulin degrading enzyme, which also degrades insulin. Therefore, the effects of insulin application on behavioral and hormonal responses and on β-endorphin degradation were tested. Pre- and post-stress levels of serum corticosterone, and post-stress plasma β-endorphin concentration differentiated between the responders and the non-responders. In brain, responders showed enhanced degradation rates of β-endorphin, assessed by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS), in hippocampal and amygdalar slices as compared to non-responders. Application of insulin to the amygdala, prior to exposure to traumatic stress, reduced post-stress anxiety and serum corticosterone levels only in the responders. In parallel, amygdalar β-endorphin degradation rate was also reduced by insulin. These results suggest that slowing down β-endorphin degradation rate may constitute an integral part of the normal stress-response, upon a failure of which an extreme anxiety develops. Modulation of opioid degradation may thus present a potential novel target for interference with extreme anxiety.

Original languageEnglish
Pages (from-to)1779-1788
Number of pages10
JournalEuropean Neuropsychopharmacology
Volume23
Issue number12
DOIs
StatePublished - Dec 2013
Externally publishedYes

Keywords

  • Acute traumatic stress
  • Anxiety
  • Insulin
  • LC-MS/MS
  • Opioid degrading enzymes
  • Rat
  • β-endorphin

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