Effects of isoflurane on learning and memory functions of wild-type and glutamate transporter type 3 knockout mice.
OBJECTIVE
General anesthetics may contribute to the post-operative cognitive dysfunction. This study was designed to determine the effects of isoflurane on the learning and memory of healthy animals or animals with a decreased brain antioxidative capacity.


METHODS
Seven- to nine-week-old female CD-1 wild-type mice or glutamate transporter type 3 (EAAT3) knockout mice whose brains have a decreased glutathione level were exposed to or were not exposed to 1.3% isoflurane for 2 h. They were subjected to fear conditioning or Barnes maze tests 1 week later.


RESULTS
The EAAT3 knockout mice had less freezing behaviour than the wild-type mice in tone-related fear. Isoflurane did not affect the freezing behaviour of the wild-type and EAAT3 knockout mice. The time for the wild-type and EAAT3 knockout mice to identify the target hole in the training sessions and memory test with the Barnes maze was not affected by isoflurane. However, the EAAT3 knockout mice took longer to identify the target hole than the wild-type mice in these tests.


CONCLUSIONS
These results suggest that EAAT3 knockout mice have significant cognitive impairment. Isoflurane may not significantly affect the cognition of wild-type and EAAT3 knockout mice in a delayed phase after isoflurane exposure.
Department of Anesthesiology, University of Virginia, Charlottesville, VA, USA.
Sunam
S
Lee
Sang-Hon
SH
Park
Zhiyi
Z
Zuo
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003072:Cognition Disorders; D050580:Excitatory Amino Acid Transporter 3 / Q000502:physiology*; D005260:Female; D007530:Isoflurane / Q000494:pharmacology*; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D050580:Excitatory Amino Acid Transporter 3; C493399:Slc1a1 protein, mouse; D007530:Isoflurane