JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taylor, D. M.
Right arrow Articles by Bickler, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taylor, D. M.
Right arrow Articles by Bickler, P. E.
Anesth Analg 1999;89:1040
© 1999 International Anesthesia Research Society

GENERAL ARTICLES

Halothane, But Not the Nonimmobilizers Perfluoropentane and 1,2-Dichlorohexafluorocyclobutane, Depresses Synaptic Transmission in Hippocampal CA1 Neurons in Rats

Donald M. Taylor, MD, PhD, Edmond I Eger, II, MD, and Philip E. Bickler, MD, PhD

Department of Anesthesia and Perioperative Care, University of California, San Francisco, California

Address correspondence and reprint requests to Dr. Donald M. Taylor, Department of Anesthesia and Perioperative Care, University of California, 513 Parnassus Ave., S-261, San Francisco, CA 94143-0648. Address e-mail to taylord{at}anesthesia.ucsf.edu


   Abstract
Top
 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Volatile anesthetics may decrease synaptic transmission at central neurons by presynaptic and/or postsynaptic actions. Nonimmobilizers are volatile compounds with lipophilicities that suggest that they should (but do not) prevent motor responses to surgical stimuli. However, nonimmobilizers interfere with learning and memory, and, thus, might be predicted to depress synaptic transmission in areas of the brain mediating memory (e.g., hippocampal CA1 neurons). To test this possibility, we stimulated the Schaffer collaterals of rat hippocampal slices and recorded from stratum pyramidale of CA1 neurons. At approximately 0.5 MAC (MAC is the minimum alveolar anesthetic concentration at one standard atmosphere that is required to eliminate movement in response to noxious stimulation in 50% of subjects), halothane decreased population spike amplitude 37% ± 21% (mean ± SD), increased latency 15% ± 9%, and decreased excitatory postsynaptic potentials 16% ± 10%. In contrast, at concentrations below (0.4 times) predicted MAC, the nonimmobilizer, 1,2 dichlorohexafluorocyclobutane (2N), slightly (not significantly) increased population spike amplitude, decreased population spike latency 9% ± 4%, and increased excitatory postsynaptic potentials 22% ± 16%. At concentrations above (2 times) predicted MAC, 2N did not significantly increase population spike, decreased latency 10% ± 4%, and did not significantly change excitatory postsynaptic potentials. At 0.1 predicted MAC, a second nonimmobilizer, perfluoropentane, tended (P = 0.05) to increase (11% ± 9%) population spike amplitude, decreased population spike latency 8% ± 2%, and tended (P = 0.06) to increase excitatory postsynaptic potentials (9% ± 8%). We conclude that clinically relevant concentrations of halothane depress synaptic transmission at Schaffer collateral-CA1 synapses and that the nonimmobilizers 2N and perfluoropentane have no effect or are excitatory. The Schaffer collateral-CA1 synapse may serve as a useful model for the production of immobility by volatile anesthetics, but is flawed as a model for the capacity of volatile anesthetics to interfere with memory and learning.

Implications: Halothane, but not the nonimmobilizers 1,2-dichlorohexafluorocyclobutane and perfluoropentane, inhibits hippocampal synaptic transmission at Schaffer collateral-CA1 synapses.


   Introduction
Top
 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Inhaled anesthetics and nonimmobilizers may provide different aspects of anesthesia. Nonimmobilizers are inhaled compounds that have a lipophilicity that indicates (as predicted by the Meyer-Overton hypothesis) that they should, but do not, prevent movement in response to a surgical stimulus (1–3). However, the nonimmobilizers 1,2 dichlorohexafluorocyclobutane (2N) and perfluoropentane (PFP) suppress a type of learning, fear-potentiated startle, in rats (4,5). Suppression occurs at partial pressures predicted to be anesthetic from the Meyer-Overton hypothesis and from the response to the volatile anesthetic, desflurane. Desflurane and the nonimmobilizers suppress fear-potentiated startle at 0.1–0.3 times minimum alveolar anesthetic concentration (MAC) or predicted MAC. Thus, conventional inhaled anesthetics suppress both movement in response to noxious stimuli and interfere with the capacity to learn, whereas nonimmobilizers only interfere with the capacity to learn.

Because the hippocampus mediates declarative memory (6–11), we considered that the nonimmobilizers might impair transmission through hippocampal CA1 neurons. If found, such impairment might suggest a mechanistic basis for the capacity of volatile compounds to interfere with memory and learning. The Schaffer collateral-CA1 synapse in the rodent hippocampal slice has been used to investigate the capacity of volatile anesthetics to depress synaptic transmission (12), and, thereby, (presumably) cause anesthesia. Volatile anesthetics may decrease transmission at this synapse by enhancing inhibition by {gamma}-aminobutyric acid (13), or by decreasing excitation by glutamate (14). Both presynaptic (15) and postsynaptic (16) mechanisms have been demonstrated, as has been a small direct depression of axonal conduction by Schaffer collateral fibers (17). We examined whether a potent inhaled anesthetic, halothane, acted similarly to or differently from the nonimmobilizers 2N and PFP.


   Methods
Top
 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
Electrophysiologic recordings were made using brain slices prepared from adult Sprague-Dawley rats (250–380 g; Simonsen Laboratories, Inc., Gilroy, CA). Rats were anesthetized with halothane and decapitated by a guillotine. Hippocampi were rapidly dissected into chilled artificial cerebrospinal fluid (aCSF). The aCSF contained (in mM) CaCl2 1.8, KCl 3.3, MgSO4 1.2, NaCl 120, NaHCO3 1.23, and dextrose 10 (Sigma, St. Louis, MO or Baker, Philipsburg, NJ, reagent grade), and was constantly aerated with a 95% O2, 5% CO2 gas mixture ("carbogen"), except as noted. Slices, nominally 500-µm thick, were prepared with either a vibratome (Pella, Inc., St. Louis, MO) or a tissue chopper (Stoelting, Wood Dale, IL), with the slicing angle oriented transverse to the long axis of the hippocampus at the temporal end. Slices were kept in a holding chamber for at least 1 h before use.

Electrophysiologic recordings were made in a submersion chamber [modified Nicoll-Alger type (18), Fine Science Tools, Foster City, CA] perfused with aCSF at room temperature (22°C ± 1°C) at about 6 mL/min. To minimize the impact of agent losses, PFP experiments were performed at a flow rate of 12 mL/min, and control recordings for these experiments also used this flow rate. Field recordings were made using glass micropipettes filled with aCSF (1–10 Mohm; Carner Glass, Claremont, CA) placed in the stratum pyramidale of CA1. Signals were amplified and filtered using an active notch filter (high pass 20 Hz, low pass corner frequency 5 Khz; Dagan, Minneapolis, MN). Individual records were collected using a digital oscilloscope (Tektronix, Beaverton, OR). Stimuli were 0.1-ms, constant voltage, rectangular pulses delivered via monopolar stainless steel electrodes placed in stratum radiatum of CA1, in the Schaffer collaterals. Evoked responses consisted of an orthodromically-evoked, negative population spike superimposed on a positive excitatory postsynaptic potential. Population spike amplitude was defined as the mean of the amplitudes of its rising and falling phases. Population spike latency was the elapsed time from stimulus to the peak of the population spike.

Control measurements were obtained after stable recordings had been obtained for a minimum of 20 min. Measurements of the effects of test compounds were obtained after at least 20 min of superfusion of the test compounds. Similarly, measurements were again obtained, usually after at least 20 min of wash, with aCSF lacking test compound. We also tested the effect of lowered O2 percentages in the absence of test compounds; we measured excitatory postsynaptic potential, and population spike amplitude and latency in four to six preparations at 75%, 50%, and 25% O2 (balance nitrogen and 5% CO2). Specific O2 concentrations were prepared by mixing 95% nitrogen/5% CO2 and 95% O2/5% CO2 with flowmeters. The resulting O2 concentrations were confirmed with measurements using a fuel-cell type analyzer (POET II; Criticare Systems, Inc., Waukesha, WI).

All values were normalized to control (preagent) values, and evaluated for significance using a paired t-test with P < 0.05 accepted for significance. We accepted one measurement for population spike amplitude, latency, and excitatory postsynaptic potentials from one slice taken from each animal. We accepted data for slices in which all values after washing returned to within 60% of control; of the 22 slices in which this criterion was met, only seven had one or more values that deviated more than 18%. Halothane (Halocarbon laboratories, River Edge, NJ) was supplied via a standard variable bypass vaporizer which yielded a partial pressure of 0.006 atmosphere absolute (ata) (i.e., a concentration of 0.6%). 2N (PCR, Inc., Gainesville, FL) was delivered by bubbling aCSF with carbogen from a tank containing a premeasured amount of liquid 2N (for a final partial pressure of 0.018 ata or approximately 0.4 times MAC predicted from its lipophilicity) (3,19) or from 2N-saturated carbogen vapor (for a final partial pressure of 0.08–0.096 ata, approximately 2 MAC). PFP (PCR, Inc.) was supplied by metering carbogen through liquid PFP to produce saturated vapor which then was bubbled through aCSF. The resulting aCSF output was diluted with liquid aCSF bubbled with plain carbogen. This yielded 0.27 ata PFP (approximately 10% of MAC predicted from its lipophilicity) (2,19). A flame ionization gas chromatograph (Gow-Mac, Bridgewater, NJ) was used to measure halothane and nonimmobilizer concentrations. The chromatograph utilized a 3.1 m stainless steel column (2.1-mm inside dimension) packed with SF-96 at 90°C; detector temperature was 195°C. The N2 carrier stream was at 12 mL/min, the detector was supplied by H2 at 38 mL/min, and air at 225 mL/min. Samples were injected through a 0.25-mL sample loop. Primary standards were produced by introducing a liquid aliquot of test compound into a flask of known volume; PFP required serial dilutions to ensure linearity of peaks.


   Results
Top
 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
At 0.006 ata (approximately half a MAC) (20), halothane consistently depressed synaptic transmission at the Schaffer collateral-CA1 synapse, as measured by decreases in population spike amplitude and excitatory postsynaptic potentials, and an increase in latency (Table 1, Figs. 1–4). Reapplication of control aCSF reversed these effects within 15 min.


View this table:
[in this window]
[in a new window]
  		Table 1. Values as Percent Change from Control Values
 


View larger version (11K):
[in this window]
[in a new window]
  		Figure 1. Field potentials were recorded from CA1 neurons in response to electrical stimulation of Schaffer-collateral fibers. The top row demonstrates the response to 0.6% halothane (middle trace) obtained in one preparation, with respective responses in the control condition and after wash of the preparation presented before and after the middle trace. The middle row similarly presents the response to 27% perfluoropentane (PFP) and the bottom row to 8% 1,2-dichlorohexafluorocyclobutane (2N).

 


View larger version (18K):
[in this window]
[in a new window]
  		Figure 2. Halothane administration at approximately 0.5 MAC (MAC is the minimum alveolar concentration at one standard atmosphere that is required to eliminate movement in response to noxious stimulation in 50% of subjects) decreased the population spike amplitude from control values. Recovery occurred with washout of the halothane. In contrast, neither 1,2-dichlorohexafluorocyclobutane (2N) nor perfluoropentane (PFP) decreased the population spike amplitude at any test concentration.

 


View larger version (16K):
[in this window]
[in a new window]
  		Figure 3. Halothane administration at approximately 0.5 MAC (MAC is the minimum alveolar concentration at one standard atmosphere that is required to eliminate movement in response to noxious stimulation in 50% of subjects) increased latency from control values. Recovery occurred with washout of the halothane. In contrast, 1,2-dichlorohexafluorocyclobutane (2N) and perfluoropentane (PFP) slightly, but significantly, decreased latency at all test concentrations.

 


View larger version (19K):
[in this window]
[in a new window]
  		Figure 4. Halothane administration at approximately 0.5 MAC (MAC is the minimum alveolar concentration at one standard atmosphere that is required to eliminate movement in response to noxious stimulation in 50% of subjects) decreased excitatory postsynaptic potentials from control values. Recovery occurred with washout of the halothane. In contrast, neither 1,2-dichlorohexafluorocyclobutane (2N) nor perfluoropentane (PFP) decreased excitatory postsynaptic potentials at any test concentration. In fact, 0.4 times the predicted MAC of 2N caused a significant (22%) increase in excitatory postsynaptic potentials.

 
Neither 0.02 ata (approximately 0.4 MAC as predicted from the oil/gas partition coefficient) (3,19) nor 0.08 ata (approximately 2 times predicted MAC) 2N decreased population spike amplitude or excitatory postsynaptic potentials, or increased latency (Table 1, Figs. 1–4). In fact, latency significantly decreased. This decrease in latency persisted after washout of 2N.

PFP at 0.27 ata (approximately 0.1 times predicted MAC) did not decrease population spike amplitude or excitatory postsynaptic potentials, or increase latency (Table 1, Figs. 1–4). In fact, as with 2N, latency significantly decreased.

The limited potency of PFP (1,2) required the application of increased partial pressures of this compound to adequately test its effect. Because the consequent decrease in O2 partial pressure might cause depression of synaptic transmission, we tested the degree of depression produced by decreasing the O2 partial pressure. Population spike and excitatory postsynaptic potential amplitudes were not decreased by a decrease in O2 partial pressure from 0.95 to 0.75 or 0.50 ata, but an observable depression was seen when the O2 partial pressure was 0.25 ata (Fig. 5).



View larger version (20K):
[in this window]
[in a new window]
  		Figure 5. Population spike amplitude was unaffected by application of 50% or 75% O2 but was depressed by 25% O2. Amplitude returned to baseline values after washing with 95% O2 (balance CO2). Similar results were obtained for excitatory postsynaptic potentials and population spike latency. Thus, any decrease in O2 produced by test compounds (1,2-dichlorohexafluorocyclobutane [2N] or perfluoropentane) would not influence the results obtained.

 

   Discussion
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
Our results differentiated among the effects of halothane and those of nonimmobilizers. Nonimmobilizers did not depress synaptic transmission at the Schaffer collateral-CA1 synapse. In contrast (and as others have observed), we found that a clinically relevant concentration of halothane depressed synaptic transmission at the Schaffer collateral-CA1 synapse. The effects seen for halothane may be mediated in one or more ways. Although a direct hyperpolarizing effect on neurons has been claimed (21), this effect is not found consistently, and it does not appear to apply to other volatile anesthetics (22,23). Volatile anesthetics may act presynaptically at this synapse to decrease action potential conduction (17) and glutamate release (14). Pre- and postsynaptic GABAergic inhibition by volatile anesthetics has also been demonstrated (16,24,25). The failure of the nonimmobilizers to depress synaptic transmission implies that nonimmobilizers may not affect neurons by the mechanisms postulated above to mediate the actions of halothane.

Our data seem to be at odds with the observation that both anesthetics and the studied nonimmobilizers interfere with learning and memory (4,5). All these compounds depress fear-potentiated startle. Because the hippocampus is a key structure in transferring items from short-term to long-term memory (26) and because amnesia is an important component of the anesthetic state, we might have predicted that halothane and the nonimmobilizers would depress transmission through the CA-1 synapse. However, volatile anesthetics do not, as a class, suppress long-term potentiation (12), which implies that this synapse may be a poor model for the amnestic effects of anesthetics.

In contrast, the CA1 synapse may serve as a model for the capacity of volatile anesthetics to produce immobility in the face of noxious stimuli. Our finding of depression of transmission by halothane, and an absence of depression by 2N and PFP, are consistent with the view that the CA1 synapse may be useful as a tool in investigations into the basis for MAC. Our findings illustrate the use of nonimmobilizers as a tool for differentiating effects of volatile anesthetics that are critical to producing insensibility to surgical stimuli from those which are not.

Our results also tend to exclude confounding factors that might have compromised interpretation of the results. Nonimmobilizers cause convulsions (3), suggesting the possibility that a stimulating effect might counterbalance a depressant effect that would otherwise have been seen. However, the partial pressure of 2N that produces convulsions is 2–3 times more than the lower of the two concentrations that we applied (0.02 ata) and 30% less than the higher partial pressure applied (0.08 ata). Despite this broad range of partial pressures and associated capacities to produce convulsive activity, no qualitative difference was seen among the effects of these two partial pressures; neither caused depression. Thus, it seems unlikely that the stimulant effects counterbalanced depressant effects that would otherwise have been seen. We also know that hypoxia might have produced depression in the studies of PFP. However, despite the decrease in O2 partial pressure that our administration of this drug caused, we did not find that PFP produced depression of transmission through the CA1 synapse.

For logistical reasons, we (and other investigators) conducted our studies at room temperature (22°C ± 1°C). At such temperatures, potency of a given anesthetic partial pressure would be increased, perhaps by as much as three- or four-fold (27). This would apply to the nonimmobilizers as well. Thus, the "MAC" values given in the Figures and Table 1 would underestimate the true MAC values. However, this would not change our basic conclusion that the anesthetic, halothane, depressed transmission, whereas the nonimmobilizers did not. Others have studied the effect of halothane and isoflurane on transmission through the hippocampus at 22°C and 35°C, finding that temperature differences minimally influence anesthetic effects on latency and population spike amplitude (28).

Finally, we note that the changes seen with 2N, especially a small decrease in latency or increase in excitatory postsynaptic potential, were sustained after washout but were not dose-dependent. This raises the question of whether the changes were real or whether, in fact, no changes really occurred. The sustained excitability after washout qualitatively parallels the changes seen with application of n-methyl-D-aspartate to the hippocampus (29). However, our conclusions are not changed by the size or sustained nature of these effects of 2N: neither 2N nor PFP depressed impulse transmission through the hippocampus, whereas halothane consistently did.


   Acknowledgments
 
Supported by National Institutes of Health Grants GM 08440, GM 47817, and GM 52212.

The authors thank Dr. Michael Laster, Dr. Pompiliu Ionescu, and Ms. Diane Gong for their gas chromatographic analyses and assistance with nonimmobilizer delivery, and Dr. Michael Halsey for discussions concerning the concepts in this study.


   Footnotes
 
Presented in part at the Association of University Anesthesiologists meeting, San Francisco, CA, May 7–9, 1998.

EIE II is a paid consultant of Baxter Pharmaceutical Products.


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Liu J, Laster MJ, Koblin DD, et al. A cut-off in potency exists in the perfluoroalkanes. Anesth Analg 1994;79:238–44.[Abstract/Free Full Text]
  2. Eger EI II, Liu J, Koblin DD, et al. Molecular properties of the "ideal" inhaled anesthetic: studies of fluorinated methanes, ethanes, propanes and butanes. Anesth Analg 1994;79:245–51.[Abstract/Free Full Text]
  3. Koblin DD, Chortkoff BS, Laster MJ, et al. Polyhalogenated and perfluorinated compounds that disobey the Meyer-Overton hypothesis. Anesth Analg 1994;79:1043–8.[Abstract/Free Full Text]
  4. Sonner J, Li J, Eger EI II. Desflurane and the nonimmobilizer 1,2-dichlorohexafluorocyclobutane suppress learning by a mechanism independent of the level of unconditioned stimulation. Anesth Analg 1998;87:200–5.[Abstract/Free Full Text]
  5. Kandel L, Chortkoff BS, Sonner J, et al. Nonanesthetics can suppress learning. Anesth Analg 1996;82:321–6.[Abstract]
  6. Fanselow MS. Modality-specific memory of fear: differential involvement of the amygdala and hippocampal formation in Pavlovian fear conditioning. In: Ono T, McNaughton BL, Molotchnikoff S, et al., eds. Perception, memory and emotion: frontiers in neuroscience. Oxford:Pergamon, 1996:499–512.
  7. Phillips RG, LeDoux JE. Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 1992;106:274–85.[Web of Science][Medline]
  8. Kim JJ, Fanselow MS. Modality specific retrograde amnesia of fear following hippocampal lesions. Science 1992;256:675–7.[Abstract/Free Full Text]
  9. Kim JJ, Rison RA, Fanselow MS. Effects of amygdala, hippocampus and periaqueductal gray lesions on short- and long-term contextual fear. Behav Neurosci 1993;107:1093–8.[Web of Science][Medline]
  10. Maren S, Fanselow MS. Synaptic plasticity in the basolateral amygdala induced by hippocampal formation stimulation in vivo. J Neurosci 1995;15:7548–64.[Abstract]
  11. Maren S, Aharonov G, Fanselow MS. Retrograde abolition of conditional fear after excitotoxic lesions of the basolateral amygdala of rats: absence of a temporal gradient. Behav Neurosci 1996;110:718–26.[Web of Science][Medline]
  12. MacIver MB, Tauck DL, Kendig JJ. General anaesthetic modification of synaptic facilitation and long-term potentiation in hippocampus. Br J Anaesth 1989;62:301–10.[Abstract/Free Full Text]
  13. Jones MV, Harrison NL. Effects of volatile anesthetics on the kinetics of inhibitory postsynaptic currents in cultured rat hippocampal neurons. J Neurophysiol 1993;70:1339–49.[Abstract/Free Full Text]
  14. Perouansky M, Baranov D, Salman M, Yaari Y. Effects of halothane on glutamate receptor-mediated excitatory postsynaptic currents: a patch-clamp study in adult mouse hippocampal slices. Anesthesiology 1995;83:109–19.[Web of Science][Medline]
  15. Miao N, Frazer MJ, Lynch C III. Volatile anesthetics depress Ca2+ transients and glutamate release in isolated cerebral synaptosomes. Anesthesiology 1995;83:593–603.[Web of Science][Medline]
  16. Tanelian DL, Kosek P, Mody I, MacIver MB. The role of the GABAA receptor/chloride channel complex in anesthesia. Anesthesiology 1993;78:757–76.[Web of Science][Medline]
  17. Mikulec AA, Pittson S, Amagasu SM, et al. Halothane depresses action potential conduction in hippocampal axons. Brain Res 1998;796:231–8.[Web of Science][Medline]
  18. Bragdon AC, Taylor DM, Wilson WA. Potassium-induced epileptiform activity in area CA3 varies markedly along the septotemporal axis of the rat hippocampus. Brain Res 1986;378:169–73.[Web of Science][Medline]
  19. Taheri S, Halsey MJ, Liu J, et al. What solvent best represents the site of action of inhaled anesthetics in humans, rats and dogs? Anesth Analg 1991;72:627–34.[Abstract/Free Full Text]
  20. White P, Johnston R, Eger EI II. Determination of anesthetic requirement in rats. Anesthesiology 1974;40:52–7.[Web of Science][Medline]
  21. Nicoll RA, Madison DV. General anesthetics hyperpolarize neurons in the vertebrate central nervous system. Science 1982;217:1055–7.[Abstract/Free Full Text]
  22. Fujiwara N, Higashi H, Nishi S, et al. Changes in spontaneous firing patterns of rat hippocampal neurons induced by volatile anaesthetics. J Physiol (Lond) 1988;402:155–75.[Abstract/Free Full Text]
  23. MacIver M, Kendig J. Anesthetic effects on resting membrane potential are voltage-dependent and agent-specific. Anesthesiology 1991;74:83–8.[Web of Science][Medline]
  24. Study RE. Isoflurane inhibits multiple voltage-gated calcium currents in hippocampal pyramidal neurons. Anesthesiology 1994;81:104–16.[Web of Science][Medline]
  25. Pearce RA. Volatile anaesthetic enhancement of paired-pulse depression investigated in the rat hippocampus. J Physiol 1996;492:823–40.[Abstract/Free Full Text]
  26. Langmoen IA, Andersen P. The hippocampal slice in vitro. In: Kerkut GA, Wheal HV, eds. Electrophysiology of isolated CNS preparations. New York:Academic Press, 1981:55–105.
  27. Regan MJ, Eger EI II. Effect of hypothermia in dogs on anesthetizing and apneic doses of inhalation agents: determination of the anesthetic index (apnea/MAC). Anesthesiology 1967;28:689–700.[Web of Science][Medline]
  28. MacIver MB, Mikulec AA, Amagasu SM, Monroe FA. Volatile anesthetics depress glutamate transmission via presynaptic actions. Anesthesiology 1996;85:823–34.[Web of Science][Medline]
  29. Anderson WW, Swartzwelder HS, Wilson WA. The NMDA receptor antagonist 2-amino-5-phosphonovalerate blocks stimulus train-induced epileptogenesis but not epileptiform bursting in the rat hippocampal slice. J Neurophysiol 1987;57:1–21.[Abstract/Free Full Text]
Accepted for publication May 20, 1999.




This article has been cited by other articles:


Home page
 Indoor and Built EnvironmentHome page
S. Nicoara, M. Culea, A. N. Nicac, E. Culea, and O. Cozarb
Selected Ion Monitoring - Gas Chromatography/Mass Spectrometry Determination of Halothane Fumes in Operating Theatres
Indoor and Built Environment, October 1, 2005; 14(5): 405 - 410.
[Abstract] [PDF]

Home page
 Anesth. Analg.Home page
R. C. Dutton, A. J. Maurer, J. M. Sonner, M. S. Fanselow, M. J. Laster, and E. I Eger II
Short-Term Memory Resists the Depressant Effect of the Nonimmobilizer 1-2-Dichlorohexafluorocyclobutane (2N) More than Long-Term Memory
Anesth. Analg., March 1, 2002; 94(3): 631 - 639.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Taylor, D. M.
Right arrow Articles by Bickler, P. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Taylor, D. M.
Right arrow Articles by Bickler, P. E.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 1999 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press