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Anesth Analg 1999;88:676
© 1999 International Anesthesia Research Society

GENERAL ARTICLES

The Effects of General Anesthetics on Excitatory and Inhibitory Synaptic Transmission in Area CA1 of the Rat Hippocampus In Vitro

Masahiro Wakasugi, MD*, Koki Hirota, MD*, Sheldon H. Roth, PhD{dagger}, and Yusuke Ito, MD*

*Department of Anesthesiology, Toyama Medical and Pharmaceutical University School of Medicine, Toyama, Japan; and {dagger}Departments of Pharmacology & Therapeutics and Anaesthesia, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada

Address correspondence and reprint requests to Dr. Hirota, Department of Anesthesiology, Toyama Medical and Pharmaceutical University School of Medicine, 2630 Sugitani, Toyama 930-0194, Japan.

It is unclear whether general anesthetics induce enhancement of neural inhibition and/or attenuation of neural excitation. We studied the effects of pentobarbital (5 x 10-4 mol/L), propofol (5 x 10-4 mol/L), ketamine (10-3 mol/L), halothane (1.5 vol%), and isoflurane (2.0 vol%) on both excitatory and inhibitory synaptic transmission in rat hippocampal slices. Excitatory or inhibitory synaptic pathways were isolated using pharmacological antagonists. Extracellular microelectrodes were used to record electrically evoked CA1 neural population spikes (PSs). In the presence of the {gamma}-aminobutyric acid type A (GABAA) receptor antagonist (bicuculline), the inhibitory actions of pentobarbital and propofol were completely antagonized, whereas those of ketamine, halothane, and isoflurane were only partially blocked. To induce the N-methyl-D-aspartate (NMDA) receptor-mediated PS (NMDA PS), the non-NMDA and GABAA receptors were blocked in the absence of Mg2+ . Ketamine, halothane, and isoflurane decreased the NMDA PS, and pentobarbital and propofol had no effect on the NMDA PS. The non-NMDA receptor-mediated PS (non-NMDA PS) was examined using the antagonists for the NMDA and GABAA receptors. Volatile, but not IV, anesthetics reduced the non-NMDA PS. These findings indicate that pentobarbital and propofol produce inhibitory actions due to enhancement in the GABAA receptor; that ketamine reduces NMDA receptor-mediated responses and enhances GABAA receptor-mediated responses; and that halothane and isoflurane modulate GABAA, NMDA, and non-NMDA receptor-mediated synaptic transmission.

Implications: Volatile anesthetics modulate both excitatory and inhibitory synaptic transmission of in vitro rat hippocampal pathways, whereas IV anesthetics produce more specific actions on inhibitory synaptic events. These results provide further support the idea that general anesthetics produce drug-specific and distinctive effects on different pathways in the central nervous system.




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Lippincott, Williams & Wilkins 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 HighWire Press
Copyright © 1999 by the International Anesthesia Research Society.