title: Amnestic concentrations of sevoflurane inhibit synaptic plasticity of hippocampal CA1 neurons through gamma-aminobutyric acid-mediated mechanisms.
abstract: BACKGROUND
  The cellular mechanisms of anesthetic-induced amnesia are still poorly understood. The current study examined sevoflurane at various concentrations in the CA1 region of rat hippocampal slices for effects on excitatory synaptic transmission and on long-term potentiation (LTP), as a possible mechanism contributing to anesthetic-induced loss of recall.
  
  
  METHODS
  Population spikes and field excitatory postsynaptic potentials were recorded using extracellular electrodes after electrical stimulation of Schaffer-collateral-commissural fiber inputs. Paired pulse facilitation was used as a measure of presynaptic effects of the anesthetic. LTP was induced using tetanic stimulation (100 Hz, 1 s). Sevoflurane at concentrations from amnestic (0.04 mm) to clinical concentrations (0.23-0.41 mm) were added to the perfusion solution.
  
  
  RESULTS
  In the presence of 0.04 mm sevoflurane, the amplitude of population spikes was significantly depressed, and tetanic stimulation induced only posttetanic potentiation and then failure of LTP. These inhibitory effects were antagonized by bicuculline (10 microm), a gamma-aminobutyric acid type A receptor antagonist. Sevoflurane at 0.23-0.41 mm further depressed the amplitude of field excitatory postsynaptic potentials in a dose-dependent manner and completely blocked LTP. Bicuculline only partially antagonized 0.41 mm sevoflurane-induced profound inhibition of LTP. Sevoflurane at 0.23-0.41 mm, but not at 0.04 mm, significantly increased paired pulse facilitation, suggesting that sevoflurane has presynaptic actions to reduce glutamate release from nerve terminals.
  
  
  CONCLUSIONS
  The current study provides evidence that amnestic concentrations of sevoflurane inhibit LTP of hippocampal CA1 neurons through gamma-aminobutyric acid-mediated mechanisms, and these actions seem to account for the effects of amnestic sevoflurane on synaptic plasticity.
authors.affiliation: Department of Anesthesiology, Gunma University Graduate School of Medicine, Maebashi City, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Ishizeki
authors.forename: Koichi
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kubo
authors.forename: Shigeru
authors.initials: S
authors.lastname: Saito
authors.forename: Fumio
authors.initials: F
authors.lastname: Goto
mesh_terms: D000647:Amnesia / Q000139:chemically induced* / Q000503:physiopathology; D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology; D008738:Methyl Ethers / Q000008:administration & dosage*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000502:physiology; D000077149:Sevoflurane; D013569:Synapses / Q000187:drug effects* / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D008738:Methyl Ethers; D011963:Receptors, GABA-A; D000077149:Sevoflurane; D005680:gamma-Aminobutyric Acid