Isoflurane Suppresses Stress-enhanced Fear Learning in a Rodent Model of Post–Traumatic Stress Disorder

Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143-0464, USA.
Anesthesiology (Impact Factor: 5.88). 03/2009; 110(3):487-95. DOI: 10.1097/ALN.0b013e3181974f3e
Source: PubMed


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

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    • "However, according to the criteria of PTSD animal models, the predator stress model, although it exhibits reduced open arm activity and reduced risk assessment behavior in the EPM test, does not show bidirectional behaviors characteristic to PTSD patients, such as numbing and pain sensitivity [37]. Similarly, in the single prolonged stress model, which consisted of restraint for 2 h, followed by forced swimming for 20 min and subsequent ether anesthesia, although the stressed animals exhibited behaviors and endocrinal feathers similar to PTSD patients, it is inappropriate for constructive validity of the effect of ether and it is not easy to mimic the re-experience [38]. There are also some reports about the modified single prolonged stress (SPS) model, which accompanied by foot shock of different intensities [39,40]. "
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