Isoflurane suppresses stress-enhanced fear learning in a rodent model of post-traumatic stress disorder

Anesthesiology. 2009 Mar;110(3):487-95. doi: 10.1097/ALN.0b013e3181974f3e.

Abstract

Background: A minority of patients who experience awareness and/or pain during surgery subsequently develop post-traumatic stress disorder. In a rodent model of post-traumatic stress disorder, stress-enhanced fear learning (SEFL), rats are preexposed to a stressor of 15 foot shocks. Subsequent exposure to a single foot shock produces an enhanced fear response. This effect is akin to sensitized reactions shown by some post-traumatic stress disorder patients to cues previously associated with the traumatic event.

Methods: The authors studied the effect of isoflurane and nitrous oxide on SEFL. Rats were exposed to the inhaled anesthetic during or after a 15-foot shock stressor. Then, rats were given a single foot shock in a different environment. Their fear response was quantified in response to the 15-foot shock and single-foot shock environments. SEFL longevity was tested by placing a 90-day period between the 15 foot shocks and the single foot shock. In addition, the intensity of the foot shock was increased to evaluate treatment effectiveness.

Results: Increasing isoflurane concentrations decreased SEFL when given during, but not after, the stressor. At 0.40 minimum alveolar concentration (MAC), isoflurane given during the stressor blocked SEFL 90 days later. A threefold increase in the stressor intensity increased the isoflurane concentration required to block SEFL to no more than 0.67 MAC. As with isoflurane, nitrous oxide suppressed SEFL at a similar MAC fraction.

Conclusions: These results suggest that sufficient concentrations (perhaps 0.67 MAC or less) of an inhaled anesthetic may prevent SEFL.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Fear / drug effects*
  • Fear / physiology
  • Fear / psychology
  • Isoflurane / pharmacology
  • Isoflurane / therapeutic use*
  • Learning / drug effects*
  • Learning / physiology
  • Male
  • Rats
  • Rats, Long-Evans
  • Stress Disorders, Post-Traumatic / etiology
  • Stress Disorders, Post-Traumatic / prevention & control*
  • Stress Disorders, Post-Traumatic / psychology
  • Stress, Psychological / etiology
  • Stress, Psychological / prevention & control*
  • Stress, Psychological / psychology

Substances

  • Isoflurane