Reduced sensitivity to ketamine and pentobarbital in mice lacking the N-methyl-D-aspartate receptor GluRepsilon1 subunit.

Anesthesia and Analgesia
Andrey B PetrenkoKenji Sakimura

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 ...Continue Reading

References

May 1, 1978·European Journal of Pharmacology·S RyderA J Trevor
May 17, 1994·European Journal of Pharmacology·F A TavernaJ F MacDonald
Oct 1, 1995·Neuropharmacology·H Mori, M Mishina
Oct 1, 1996·British Journal of Anaesthesia·K Hirota, D G Lambert
Nov 7, 1998·Anesthesia and Analgesia·R Kohrs, M E Durieux
Aug 28, 1999·Progress in Neurobiology·T Yamakura, K Shimoji
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·T YamakuraR A Harris
Jun 12, 2001·Current Opinion in Neurobiology·S Cull-CandyM Farrant
May 28, 2003·Neuroscience Research·Andrei B PetrenkoKenji Sakimura

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Citations

Jul 12, 2008·International Anesthesiology Clinics·Stuart A Forman, Victor A Chin
May 28, 2009·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Rodrigo Machado-VieiraCarlos A Zarate
Jan 23, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Xiangdong ChenDouglas A Bayliss
Sep 10, 2010·Harvard Review of Psychiatry·Carlos ZarateGiacomo Salvadore
Dec 18, 2013·European Journal of Pharmacology·Andrey B PetrenkoHiroshi Baba
Jan 18, 2014·L'Encéphale·P De MaricourtR Gaillard
Apr 29, 2009·Pharmacology & Therapeutics·Rodrigo Machado-VieiraCarlos A Zarate
Dec 15, 2016·Frontiers in Human Neuroscience·Linda Li, Phillip E Vlisides
May 11, 2018·Brain and Behavior·Yunluo LvYinming Zeng
Jun 24, 2008·European Journal of Anaesthesiology·Y FuY Ma
Jul 27, 2017·Proceedings of the National Academy of Sciences of the United States of America·Francisco J FloresPatrick L Purdon
Aug 14, 2015·Journal of Neural Engineering·Francisco J FloresEmery N Brown
Dec 27, 2011·Neuropharmacology·Caroline E McCardle, Sarah E Gartside
Oct 6, 2011·Pharmacology, Biochemistry, and Behavior·Rodrigo Machado-VieiraCarlos A Zarate

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