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Related Experiment Video

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Extinction Training During the Reconsolidation Window Prevents Recovery of Fear
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Prophylactic Ketamine Attenuates Learned Fear.

Josephine C McGowan1,2, Christina T LaGamma2,3, Sean C Lim3

  • 1Doctoral Program in Neurobiology and Behavior, Columbia University, New York, NY, USA.

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
|January 28, 2017
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Summary

Administering ketamine one week before a stressor can prevent fear responses in mice. Ketamine is not effective when given immediately before or after stress, suggesting a prophylactic role.

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Behavioral Science

Background:

  • Ketamine shows antidepressant effects for major depressive disorder and posttraumatic stress disorder.
  • Previous research indicates ketamine's prophylactic potential against stress-induced depressive behaviors in mice.

Purpose of the Study:

  • To determine the optimal timing for ketamine administration relative to a stressor to maximize antidepressant and prophylactic effects.
  • To investigate if ketamine can provide prophylaxis against subsequent stressors.

Main Methods:

  • Mice received a single dose of ketamine (30 mg/kg) or saline at various time points before or after contextual fear conditioning (CFC).
  • Fear expression and reactivation were assessed using behavioral measures like freezing and rearing.

Main Results:

  • Prophylactic ketamine administered one week prior to CFC reduced freezing behavior.
  • Ketamine given 1 hour or 1 month before CFC, or after CFC/during extinction, did not alter fear expression.
  • Ketamine before reinstatement increased rearing, suggesting enhanced attentiveness.

Conclusions:

  • Ketamine can buffer fear responses when administered prophylactically one week before a stressor.
  • Immediate pre- or post-stress administration of ketamine is ineffective in altering fear responses.
  • Clinical use of ketamine may benefit from a prophylactic administration strategy one week before anticipated stressors.