JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Eger, E. I Articles by Sonner, J. M. Search for Related Content PubMed PubMed Citation Articles by Eger, E. I, II Articles by Sonner, J. M. Related Collections Mechanisms Pharmacology

---

ANESTHETIC PHARMACOLOGY

Isoflurane Antagonizes the Capacity of Flurothyl or 1,2-Dichlorohexafluorocyclobutane to Impair Fear Conditioning to Context and Tone

Edmond I Eger, II, MD^*, Yilei Xing, MD^*, Robert Pearce, MD, Steven Shafer, MD, Michael J. Laster, DVM^*, Yi Zhang, MD^*, Michael S. Fanselow, PhD, and James M. Sonner, MD^*

*Department of Anesthesia and Perioperative Care, University of California, San Francisco, California; Department of Anesthesiology, University of Wisconsin, Madison, Wisconsin; Department of Anesthesiology, Stanford University, Stanford, California; and Department of Psychology, University of California, Los Angeles, California

Address correspondence and reprint requests to Dr. Edmond I Eger II, Department of Anesthesia, S-455, University of California, San Francisco, CA 94143-0464. Address e-mail to egere{at}anesthesia.ucsf.edu

In animals, the conventional inhaled anesthetic, isoflurane, impairs learning fear to context and fear to tone, doing so at concentrations that produce amnesia in humans. Nonimmobilizers are inhaled compounds that do not produce immobility in response to noxious stimulation, nor do they decrease the requirement for conventional inhaled anesthetics. Like isoflurane, the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (2N) impairs learning at concentrations less than those predicted from its lipophilicity to produce anesthesia. The capacity of the nonimmobilizer di-(2,2,2,-trifluoroethyl) ether (flurothyl) to affect learning and memory has not been studied. Both nonimmobilizers can cause convulsions. We hypothesized that if isoflurane, 2N, and flurothyl act by the same mechanism to impair learning and memory, their effects should be additive. We found that isoflurane, 2N, and flurothyl (each, alone) impaired learning fear to context and fear to tone in rats, with the nonimmobilizers doing so at concentrations less than those that cause convulsions. (Fear was defined by freezing [volitional immobility] in the presence of the conditioned stimulus [context or tone].) However, the combination of isoflurane and 2N or flurothyl produced an antagonistic rather than an additive effect on learning, a finding in conflict with our hypothesis. And flurothyl was no less potent than 2N (at least no less potent relative to the concentration of each that produced convulsions) in its capacity to impair learning. We conclude that conventional inhaled anesthetics and nonimmobilizers impair learning and memory by different mechanisms. The basis for this impairment remains unknown.

IMPLICATIONS: Conventional inhaled anesthetics and nonimmobilizers are antagonistic in their effects on learning and memory, and this finding suggests that they impair learning and memory, at least in part, by different mechanisms.

This article has been cited by other articles:

				E. D. Zarnowska, R. A. Pearce, A. A. Saad, and M. Perouansky The {gamma}-Subunit Governs the Susceptibility of Recombinant {gamma}-Aminobutyric Acid Type A Receptors to Block by the Nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, 2N) Anesth. Analg., August 1, 2005; 101(2): 401 - 406. [Abstract] [Full Text] [PDF]

				M. Liao, J. M. Sonner, R. Jurd, U. Rudolph, C. M. Borghese, R. A. Harris, M. J. Laster, and E. I. Eger II {beta}3-Containing Gamma-Aminobutyric AcidA Receptors Are Not Major Targets for the Amnesic and Immobilizing Actions of Isoflurane Anesth. Analg., August 1, 2005; 101(2): 412 - 418. [Abstract] [Full Text] [PDF]

				J. M. Sonner, M. Cascio, Y. Xing, M. S. Fanselow, J. E. Kralic, A. L. Morrow, E. R. Korpi, S. Hardy, B. Sloat, E. I. Eger II, et al. {alpha}1 Subunit-Containing GABA Type A Receptors in Forebrain Contribute to the Effect of Inhaled Anesthetics on Conditioned Fear Mol. Pharmacol., July 1, 2005; 68(1): 61 - 68. [Abstract] [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999