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This article describes the effect of isoflurane on amino acid release and tissue content induced by energy deprivation in slices of rat hippocampus. Energy deprivation (95% N2/ 5% CO2 and glucose free medium) (ED) induced an increase in the release of all amino acids measured, with the exception of glutamine. The tissue content of all amino acids except γ-aminobutyric acid (GABA) and arginine was concomitantly reduced. Isoflurane (1.5% and 3.0%) reduced glutamate release during ED by 27% and 28% (p < 0.05 as compared with release without isoflurane), respectively, whereas the tissue content was slightly increased. Similarly, GABA release was reduced by 25% and 25% (p < 0.05 as compared with release without isoflurane) accompanied by an insignificant enhancement in tissue content as compared with ED without isoflurane. Isoflurane reduced the release of taurine and most of the other amino acids. The total amount of all amino acids (both released and retained) was not significantly altered by the anesthetic. These observations demonstrate that isoflurane can modify the changes in amino acid handling induced by energy deprivation.