Halothane, but not the nonimmobilizers perfluoropentane and 1,2-dichlorohexafluorocyclobutane, depresses synaptic transmission in hippocampal CA1 neurons in rats.
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.


CONCLUSIONS
Halothane, but not the nonimmobilizers 1,2-dichlorohexafluorocyclobutane and perfluoropentane, inhibits hippocampal synaptic transmission at Schaffer collateral-CA1 synapses.
Taylor
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Department of Anesthesia and Perioperative Care, University of California, San Francisco 94143-0648, USA. taylord@anesthesia.ucsf.edu
Eger
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Bickler
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PE
D000200:Action Potentials / Q000187:drug effects; D000777:Anesthetics / Q000008:administration & dosage / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D017402:Chlorofluorocarbons / Q000008:administration & dosage / Q000494:pharmacology*; D003503:Cyclobutanes / Q000008:administration & dosage / Q000494:pharmacology*; D004195:Disease Models, Animal; D005071:Evoked Potentials / Q000187:drug effects; D005466:Fluorocarbons / Q000008:administration & dosage / Q000494:pharmacology*; D006221:Halothane / Q000008:administration & dosage / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D007858:Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013569:Synapses / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects*; D010420:Pentanes
D000777:Anesthetics; D018685:Anesthetics, Inhalation; D017402:Chlorofluorocarbons; D003503:Cyclobutanes; D005466:Fluorocarbons; D006221:Halothane; C090640:1,2-dichloro-1,2,3,3,4,4-hexafluorocyclobutane; C008806:perfluoropentane; D010420:Pentanes