Immediate ketamine treatment does not prevent posttraumatic stress responses in an animal model for PTSD

Alzbeta Juven-Wetzler, Hagit Cohen, Zeev Kaplan, Avi Kohen, Oren Porat, Joseph Zohar

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Clinical studies suggest that administration of ketamine hydrochloride-an antagonist at the N-methyl. d-aspartate ionophore-provides short-term amelioration for depressive symptoms. The effects of a brief course of ketamine given immediately following exposure to psychogenic stress on the behavioral stress responses were assessed in an animal model of posttraumatic stress disorder. Animals exposed to stress were treated 1. h later with ketamine (0.5, 5, and 15. mg/kg) or vehicle for three days (N=107). Outcome measures included behavior in the elevated plus maze (EPM) and acoustic startle response (ASR) tests 30 days after initial exposure and freezing behavior upon exposure to a trauma-cue on day 31. Pre-set cut-off behavioral criteria classified exposed animals according to their EPM and ASR response-patterns into "extreme," "minimal," or "partial" behavioral response for analysis of prevalence rates of "PTSD-like behavior." Circulating corticosterone levels were assessed 20. min after injection of ketamine in exposed and unexposed animals (N=62). The dexamethasone suppression test was used to assess negative feedback inhibition of the HPA axis. Prevalence rates of extremely-, partially-, or minimally-disrupted behavior demonstrated that ketamine administered immediately following stress exposure was ineffective in alleviating "PTSD-like behavior" at day 30 after exposure. Administration of ketamine was associated with increase in freezing behavior after exposure to a trauma-cue on day 31. Corticosterone levels were significantly suppressed by ketamine only in the exposed animals. Administration of ketamine immediately following trauma-exposure may not only be ineffective but actually detrimental in the long term. A disruption of the post-stress HPA-response has been raised as a contributing factor.

Original languageEnglish
Pages (from-to)469-479
Number of pages11
JournalEuropean Neuropsychopharmacology
Volume24
Issue number3
DOIs
StatePublished - 1 Mar 2014
Externally publishedYes

Keywords

  • Animal model
  • Early drug intervention
  • Extreme/minimal behavioral response
  • Ketamine
  • Post-traumatic stress disorder
  • Secondary prevention

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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