Changes in anesthetic sensitivity and glutamate receptors in the aging canine brain.
This study investigated whether the aging process in dogs is associated with an increased sensitivity to inhalation anesthesia and whether age-related changes in glutamate receptors are related to the increased sensitivity. The mean minimum alveolar concentration (MAC) of isoflurane was 1.82 +/- .08% for 2-3 year olds and 1.45 +/- .06% for 11 years olds, indicating that there was an increased potency of isoflurane in the older dogs as compared to the young. These older animals also showed a significant decrease in binding of [3H]glutamate and [3H]dizocilpine ([3H]MK801) to N-methyl-D-aspartate (NMDA) receptors in multiple cortical and hippocampal regions. The density of binding to NMDA receptors in the cortex, using a single concentration of ligand, correlated significantly with individual MAC values. These results demonstrate that dogs experience an increase in anesthetic potency with increased age, similar to humans, and that age-related changes in the NMDA receptor may represent one mechanism underlying this increased sensitivity to anesthesia.
Magnusson
K R
KR
Department of Anatomy & Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523-1670, USA. kmagnuss@lamar.colostate.edu
Scanga
C
C
Wagner
A E
AE
Dunlop
C
C
D000375:Aging; D000704:Analysis of Variance; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007530:Isoflurane / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D019275:Radiopharmaceuticals; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D014316:Tritium
D018685:Anesthetics, Inhalation; D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D019275:Radiopharmaceuticals; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D007530:Isoflurane