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Spontaneous hyperactivity in mutant mice lacking the NMDA receptor GluRε1 subunit is aggravated during exposure to 0.1 MAC sevoflurane and is preserved after emergence from sevoflurane anaesthesia

Published online by Cambridge University Press:  01 December 2008

A. B. Petrenko ,
T. Kohno ,
J. Wu ,
K. Sakimura  and
H. Baba
A. B. Petrenko*
Affiliation:
Niigata University Graduate School of Medical and Dental Sciences, Division of Anesthesiology, Niigata, Japan
T. Kohno
Affiliation:
Niigata University Graduate School of Medical and Dental Sciences, Division of Anesthesiology, Niigata, Japan
J. Wu
Affiliation:
Niigata University Graduate School of Medical and Dental Sciences, Division of Anesthesiology, Niigata, Japan
K. Sakimura
Affiliation:
Niigata University, Brain Research Institute, Department of Cellular Neurobiology, Niigata, Japan
H. Baba
Affiliation:
Niigata University Graduate School of Medical and Dental Sciences, Division of Anesthesiology, Niigata, Japan
*
Correspondence to: Andrey B. Petrenko, Division of Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Asahimachi 1-757, Niigata 951-8510, Japan. E-mail: abpetr@med.niigata-u.ac.jp; Tel: +81 25 227 2328; Fax: +81 25 227 0790
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Summary

Background and objective

Patients who awake from sevoflurane anaesthesia with symptoms of agitation may have some underlying functional substrate that is sensitive to the low concentrations of anaesthetic encountered during emergence. One candidate for such a substrate could be neurocircuitry implied in the pathophysiology of both agitation and movement disorders with hyperactivity. We postulated that hyperactive animals would show a further increase in activity in the presence of low concentrations of volatile anaesthetics, such as sevoflurane.

Methods

To confirm our hypothesis, we examined the effects of two subanaesthetic concentrations of sevoflurane, isoflurane and halothane (0.1 and 0.2 MAC (minimum alveolar concentration)) on spontaneous activity in N-methyl-d-aspartate receptor GluRε1 subunit knockout mice exhibiting locomotor hyperactivity in a novel environment and compared these results with those for wild-type controls. We also compared the effects of anaesthetic concentrations of sevoflurane (1.2 MAC) on mice activity during postanaesthesia recovery.

Results

Out of the three anaesthetics used, only sevoflurane administered at 0.1 MAC caused a significantly different response between the two experimental groups. Exposure to this subanaesthetic concentration of sevoflurane reduced the activity of wild-type mice, whereas mutant animals showed a further increase in hyperactivity. The effects of 1.2 MAC sevoflurane anaesthesia on mice activity during postanaesthesia recovery also differed significantly between the two genotypes. Exposure to anaesthetic concentrations of sevoflurane had a sedative effect on wild-type mice, whereas mutant mice preserved their high levels of activity upon emergence from the anaesthesia.

Conclusions

The presence of an inherent anomaly in mutant mice that becomes more manifest during exposure to 0.1 MAC sevoflurane and is still present after the emergence from sevoflurane anaesthesia suggests the presence of and necessitates a search for some putative substrate that may, by analogy, underlie emergence agitation in the clinical setting.

Keywords

ANAESTHETICS INHALATION, sevofluraneNMDA RECEPTORSGluRε1KNOCKOUT MICELOCOMOTOR ACTIVITY, drug effects
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 12 , December 2008 , pp. 953 - 960
Copyright
Copyright © European Society of Anaesthesiology 2008

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