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Reduced sensitivity to ketamine and pentobarbital in mice lacking the N-methyl-D-aspartate receptor GluRepsilon1 subunit.
- Source :
-
Anesthesia and analgesia [Anesth Analg] 2004 Oct; Vol. 99 (4), pp. 1136-1140. - Publication Year :
- 2004
-
Abstract
- Ketamine is an IV anesthetic with N-methyl-d-aspartate receptor (NMDAR)-blocking properties. However, it is still unclear whether ketamine's general anesthetic actions are mediated primarily via blockade of NMDAR. Functional NMDARs are composed by the assembly of a GluRzeta1 (NR1) subunit with GluRepsilon (GluRepsilon1-4; NR2A-D) subunits, which confer unique properties on native NMDARs. We hypothesized that animals deficient in GluRepsilon1, an abundant and ubiquitously postnatally expressed NMDAR subunit, might be resistant to the effects of ketamine. Here, we evaluated a righting reflex to determine the general anesthetic/hypnotic potency of ketamine administered intraperitoneally to GluRepsilon1 knockout mice and compared these results with those for wild-type mice. Mutant mice were more resistant to ketamine than control mice. Unexpectedly, mutant mice were also more resistant to pentobarbital, which is thought not to interact with NMDAR at clinically relevant concentrations. Although these data in no way eliminate the possibility of the involvement of the NMDAR GluRepsilon1 subunit in mediation of ketamine anesthesia/hypnosis, they suggest the difficulties with interpretation of altered anesthetic sensitivity in knockout animal models.
- Subjects :
- Anesthetics, Dissociative pharmacokinetics
Animals
Biotransformation
Brain metabolism
Hypnotics and Sedatives pharmacokinetics
Injections, Intraperitoneal
Ketamine pharmacokinetics
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mutation genetics
Mutation physiology
Pentobarbital pharmacokinetics
Reflex drug effects
Anesthetics, Dissociative pharmacology
Hypnotics and Sedatives pharmacology
Ketamine pharmacology
Pentobarbital pharmacology
Receptors, N-Methyl-D-Aspartate genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0003-2999
- Volume :
- 99
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Anesthesia and analgesia
- Publication Type :
- Academic Journal
- Accession number :
- 15385364
- Full Text :
- https://doi.org/10.1213/01.ANE.0000131729.54986.30