Changes in anesthetic sensitivity and glutamate receptors in the aging canine brain

This study investigated whether the aging process in dogs is associated wit h an increased sensitivity to inhalation anesthesia and whether age-related changes in glutamate receptors are related to the increased sensitivity. T he mean minimum alveolar concentration (MAC) of isoflurane was 1.82 +/- .08 % for 2-3 year olds and 1.45 +/- .06% for 11 Sears olds, indicating that th ere was an increased potency of isoflurane in the older dogs as compared to the young. These older animals also showed a significant decrease in bindi ng of [H-3]glutamate and [H-3]dizocilpine ([H-3]MK801) to N-methyl-D-aspart ate (NMDA) receptors in multiple cortical and hippocampal regions. The dens ity of binding to NMDA receptors in the cortex, using a single concentratio n of ligand, correlated significantly with individual MAC values. These res ults demonstrate that dogs experience an increase in anesthetic potency wit h increased age, similar to humans, and that age-related changes in the NMD A receptor may represent one mechanism underlying this increased sensitivit y to anesthesia.