Spatial memory using active allothetic place avoidance in adult rats after isoflurane anesthesia: a potential model for postoperative cognitive dysfunction

J Neurosurg Anesthesiol. 2011 Apr;23(2):138-45. doi: 10.1097/ANA.0b013e3182049f19.


Background: We described a paradigm of active allothetic place avoidance (AAPA) as a measure of spatial memory in adult rats. We hypothesized that, pending successful AAPA training, treatment with isoflurane would trigger spatial memory deficits.

Methods: Fifteen of 20 adult rats were successfully trained and randomly allocated to control and isoflurane treatment groups. An additional 7 animals were used to demonstrate hemodynamic stability during general anesthesia. After training, experimental animals received a 2-hour isoflurane anesthetic. General endotracheal anesthesia was maintained at an isoflurane concentration of 1.8% to 2%. After intervention, retention of training was tested on postanesthesia days 1, 3, and 7.

Results: Animals treated with isoflurane displayed selected spatial memory changes up to postanesthesia day 7. There were 2 findings of decreased active avoidance behavior in rats receiving isoflurane: a significant (P=0.029) reduction in maximum path of avoidance in the isoflurane-treated rats compared with controls, and a significant (P=0.038) increase in total path length in the controls. No other measured AAPA parameters achieved statistical significance.

Conclusions: Control animals demonstrated increased active avoidance behavior in the AAPA task compared with isoflurane-treated animals. Animals exposed to 2-hour isoflurane general anesthetic had a reduction in the maximum path of avoidance measure up to 7 days postanesthesia, whereas gross spatial parameters such as number of entrances into the shock zone were not significantly different between groups. The AAPA model may prove useful in ascertaining the learning and memory deficits of postoperative cognitive dysfunction.

MeSH terms

  • Anesthesia, Inhalation*
  • Anesthetics, Inhalation*
  • Animals
  • Avoidance Learning / drug effects*
  • Cognition Disorders / chemically induced
  • Cognition Disorders / psychology*
  • Disease Models, Animal
  • Hemodynamics / physiology
  • Isoflurane*
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects*
  • Postoperative Complications / chemically induced
  • Postoperative Complications / psychology*
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Space Perception / drug effects*
  • Telemetry


  • Anesthetics, Inhalation
  • Isoflurane