Volatile anesthetic requirements differ in mice selectively bred for sensitivity or resistance to diazepam: implications for the site of anesthesia.

Abstract:

:One approach to elucidating the general anesthetic target has used genetic selection procedures, wherein animals are bred for sensitivity or resistance to general anesthetics and correlations are sought with a specific neuronal structural or functional defect. For example, murine strains have been developed that are either sensitive or resistant to the obtunding effects of diazepam, as assessed by their ability to maintain balance on a rotating rod. The present study explored whether diazepam-sensitive (DS) and diazepam-resistant (DR) mice might also be similarly divergent in the obtunding response to general anesthetics, by testing the requirements for halothane and enflurane in these strains. Using a carousel enclosed in a chamber, the end-point of loss-of-righting reflex was defined. For both anesthetics, the DS groups had a lower median effective dose (ED50, %atm) than did the DR group, and the reductions paralleled diazepam susceptibility. For example, with halothane, the ED50 for the DS group was 0.72 +/- 0.022 (SE); the ED50 for the DR group was 0.87 +/- 0.030 (P < 0.0001). Similar results were obtained with enflurane. Such findings associate an inbred difference in response to diazepam with altered volatile anesthetic requirement, suggesting that these two phenotypes are mediated by a common underlying mechanism.

journal_name

Anesth Analg

journal_title

Anesthesia and analgesia

authors

McCrae AF,Gallaher EJ,Winter PM,Firestone LL

doi

10.1213/00000539-199376060-00022

subject

Has Abstract

pub_date

1993-06-01 00:00:00

pages

1313-7

issue

6

eissn

0003-2999

issn

1526-7598

journal_volume

76

pub_type

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