Isoflurane causes anterograde but not retrograde amnesia for pavlovian fear conditioning.
BACKGROUND
Production of retrograde amnesia by anesthetics would indicate that these drugs can disrupt mechanisms that stabilize memory. Such disruption would allow suppression of memory of previous untoward events. The authors examined whether isoflurane provides retrograde amnesia for classic (Pavlovian) fear conditioning.


METHODS
Rats were trained to fear tone by applying three (three-trial) or one (one-trial) tone-shock pairs while breathing various constant concentrations of isoflurane. Immediately after training, isoflurane administration was either discontinued, maintained unchanged, or rapidly increased to 1.0 minimum alveolar concentration for 1 h longer. Groups of rats were similarly trained to fear context while breathing isoflurane by applying shocks (without tones) in a distinctive environment. The next day, memory for the conditioned stimuli was determined by presenting the tone or context (without shock) and measuring the proportion of time each rat froze (appeared immobile). For each conditioning procedure, the effects of the three posttraining isoflurane treatments were compared.


RESULTS
Rapid increases in posttraining isoflurane administration did not suppress conditioned fear for any of the training procedures. In contrast, isoflurane administration during conditioning dose-dependently suppressed conditioning (P < 0.05). Training to tone was more resistant to the effects of isoflurane than training to context (P < 0.05), and the three-trial learning procedure was more was more resistant than the one-trial procedure (P < 0.05).


CONCLUSIONS
Isoflurane provided intense dose-dependent anterograde but not retrograde amnesia for classic fear conditioning. Isoflurane appears to disrupt memory processes that occur at or within a few minutes of the conditioning procedure.
Dutton
Robert C
RC
Department of Anesthesia and Perioperative Care, University of California-San Francisco, San Francisco, California 94143-0464, USA. duttonr@anesthesia.ucsf.edu
Maurer
Anya J
AJ
Sonner
James M
JM
Fanselow
Michael S
MS
Laster
Michael J
MJ
Eger
Edmond I
EI
D000161:Acoustic Stimulation; D020324:Amnesia, Anterograde / Q000139:chemically induced* / Q000523:psychology; D000648:Amnesia, Retrograde / Q000139:chemically induced* / Q000523:psychology; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003214:Conditioning, Classical / Q000187:drug effects*; D005239:Fear / Q000523:psychology*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D007530:Isoflurane