Neuropharmacology and Analgesia Isoflurane and sevoflurane dose-dependently impair hippocampal long-term potentiation Rainer Haseneder a, ⁎, Stephan Kratzer a , Ludwig von Meyer b , Matthias Eder c , Eberhard Kochs a , Gerhard Rammes a a Department of Anaesthesiology, Klinikum rechts der Isar, Technische Universität München, Ismaninger Straße 22, 81675 Munich, Germany b Institute of Legal Medicine, Ludwig-Maximillians-Universität München, Frauenlobstraße 7a, 80337 Munich, Germany c Research Group Neuronal Network Dynamics, Max Planck Institute of Psychiatry, Kraepelinstraße 2-10, 80804 Munich, Germany abstract article info Article history: Received 22 June 2009 Received in revised form 1 September 2009 Accepted 8 September 2009 Available online 16 September 2009 Keywords: Isoflurane Sevoflurane Synaptic plasticity Long-term potentiation Hippocampus Isoflurane and sevoflurane are commonly used volatile anaesthetics. Although acting via similar cellular mechanisms, the effect of different volatile anaesthetics on synaptic plasticity might differ. In the present study, using acute murine brain slice preparations, we compared the effects of isoflurane and sevoflurane on synaptic transmission and synaptic plasticity (long-term potentiation, LTP) in the CA1 stratum radiatum of the hippocampus. Isoflurane and sevoflurane dose-dependently diminished excitatory postsynaptic field potentials. In the presence of isoflurane (sevoflurane) at concentrations of 0.19, 0.28 and 0.37 mM (0.11, 0.21 and 0.42 mM), which correspond to 0.7-, 1.0- and 1.4-fold (0.3-, 0.6- and 1.1-fold) minimum alveolar concentration (MAC), high frequency stimulation reliably induced LTP. When isoflurane (sevoflurane) was applied at concentrations of 0.56 and 0.74 mM (0.63 and 0.84 mM), which equal 2.1- and 2.7-fold (1.7- and 2.2-fold) MAC, LTP was blocked. Our results indicate, that both anaesthetics influence synaptic strength to a similar degree, with only high concentrations blocking hippocampal CA1 stratum radiatum long-term potentiation. © 2009 Elsevier B.V. All rights reserved. 1. Introduction The molecular mechanisms of the volatile anaesthetics isoflurane and sevoflurane are still a matter of debate (reviews: Campagna et al., 2003; Rudolph and Antkowiak, 2004). Studies using various in vitro expression systems showed that both isoflurane and sevoflurane potentiate γ-aminobutyric acid type A and glycine receptor function, and inhibit nicotinic acetylcholine, α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid, and N-methyl-D-aspartate receptors (review: Campagna et al., 2003). Both anaesthetics depress synaptic transmis- sion in hippocampal slice preparations (Hirota et al., 1998; Sasaki et al., 2002), at least in part by an activation of γ-aminobutyric acid type A receptors (Hirota et al., 1998). In contrast to the considerable amount of studies dealing with the effect of volatile anaesthetics on isolated receptor function or on synaptic transmission, there is only marginal knowledge about the impact of volatile anaesthetics on synaptic plasticity. Long-term potentiation (LTP), an alteration of synaptic strength and, thus, one facet of synaptic plasticity, is widely assumed to be a correlate for memory consolidation and recall (review: Bliss and Collingridge, 1993). LTP can be induced by activating synapses briefly at high frequencies. It has been suggested, that blockade of synaptic plasticity during anaesthesia might account for postoperative cogni- tive deficit and/or intraoperative amnesia (Ishizeki et al., 2008; Simon et al., 2001). Profound amnestic properties of anaesthetic agents are a desirable pharmacological characteristic, as lack of intraoperative amnesia might result in unwanted cases of recall. Although acting via similar cellular mechanisms, the effect of different volatile anaesthetics on synaptic plasticity might differ. MacIver et al. (1989) reported that halothane reduces the probability of LTP induction in hippocampal CA1 pyramidal neurons, whereas methoxyflurane does not block LTP. In the present work, we therefore compared the effect of two commonly used volatile anaesthetics, isoflurane and sevoflurane, on synaptic transmission and synaptic plasticity in an acute murine hippocampal slice preparation. 2. Methods 2.1. Brain slice preparation The experimental protocols were approved by the Ethical Committee on Animal Care and Use of the Government of Bavaria, Germany. After killing male CD1 mice (d20–30) by cervical disloca- tion, their brains were rapidly removed, and sagittal slices (350 μm thick) comprising the hippocampus were prepared in ice-cold artificial cerebrospinal fluid (aCSF) using a vibroslicer (HM 650 V, Microm International, Walldorf, Germany). Slices were allowed to European Journal of Pharmacology 623 (2009) 47–51 ⁎ Corresponding author. Tel.: +49 89 30622 256; fax: +49 89 30622 402. E-mail address: haseneder@mpipsykl.mpg.de (R. Haseneder). 0014-2999/$ – see front matter © 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.ejphar.2009.09.022 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar