title: Changes in anesthetic sensitivity and glutamate receptors in the aging canine brain.
abstract: 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.
authors.affiliation: Department of Anatomy & Neurobiology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523-1670, USA. kmagnuss@lamar.colostate.edu
authors.forename: K R
authors.initials: KR
authors.lastname: Magnusson
authors.forename: C
authors.initials: C
authors.lastname: Scanga
authors.forename: A E
authors.initials: AE
authors.lastname: Wagner
authors.forename: C
authors.initials: C
authors.lastname: Dunlop
mesh_terms: 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
chemical_list: 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