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ANESTHETIC PHARMACOLOGY

Intravenous Anesthetics Are More Effective than Volatile Anesthetics on Inhibitory Pathways in Rat Hippocampal CA1

Takehisa Asahi, MD^*, Koki Hirota, MD, PhD^*, Rika Sasaki, MD, PhD^*, Yamazaki Mitsuaki, MD, PhD^*, and Sheldon H. Roth, PhD

*Department of Anesthesiology, University of Toyama, Japan; and Departments of Pharmacology & Therapeutics and Anaesthesia, Faculty of Medicine, University of Calgary, Alberta, Canada

Address correspondence and reprint requests to Takehisa Asahi, MD, Department of Anesthesiology, University of Toyama, 2630 Sugitani, Toyama-city, Toyama, 930-0194 Japan. Address e-mail to take3260{at}ms.toyama-mpu.ac.jp.

In this study, we have examined the effects of both volatile and IV general anesthetics on excitatory synaptic transmission, with and without recurrent inhibition, to clarify whether excitatory or inhibitory synapses are the major targets of action. Field population spike amplitudes (fPSs) of CA1 pyramidal neurons were recorded in rat hippocampal slices. Schaffer-collateral-commissural fibers (Sch) were stimulated orthodromically, and the evoked fPSs (PS[Sch]) in CA1 area were measured. In addition, the fPSs (PS[Alv+Sch]) elicited by stimulation of the Sch after antidromic stimulation of the alveus hippocampi (Alv) to produce recurrent inhibition were determined. It was observed that sevoflurane (0.5%–5%) and isoflurane (0.5%–5%) primarily inhibited PS[Sch] and also produced additive inhibition on the PS[Alv+Sch] in a concentration-dependent manner. The calculated 50% effective concentration (EC₅₀) values for PS[Sch] and PS[Alv+Sch] were 5.3 vol% and 3.9 vol% (sevoflurane) and 1.7 vol% and 1.1 vol% (isoflurane), respectively. In comparison, thiopental (2.0 x 10^–5–5.0 x 10^–4 mol/L) reduced both the PS[Sch] and PS[Alv+Sch] in a concentration-dependent manner. The calculated EC₅₀ values for thiopental on PS[Sch] and PS[Alv+Sch] were 3.4 x 10^–4 and 5.7 x 10^–5 mol/L, respectively. Propofol (2.0 x 10^–5–3.5 x 10^–4 mol/L) had little effect on the PS[Sch] but reduced PS[Alv+Sch] with a calculated EC₅₀ value of 5.1 x 10^–4 mol/L. The effects of the IV anesthetics with recurrent inhibition were antagonized in the presence of the -aminobutyric acid-A-receptor antagonist bicuculline methiodide. In addition, all anesthetics prolonged recurrent inhibition from 100 ms (sevoflurane and isoflurane) to 400 ms (propofol). The results suggest that sevoflurane and isoflurane inhibit mainly on glutamate-mediated orthodromic pathways, whereas thiopental and propofol enhance -aminobutyric acid-A-mediated recurrent inhibitory pathways in CA1 neurons, thus providing further evidence that the mechanisms of general anesthetics are drug- and pathway-specific.

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