PMID: 15220773Jun 29, 2004Paper

Effects on synaptic inhibition in the hippocampus do not underlie the amnestic and convulsive properties of the nonimmobilizer 1,2-dichlorohexafluorocyclobutane

Anesthesiology
M Perouansky, R A Pearce

Abstract

Although it does not suppress movement in response to noxious stimuli, the nonimmobilizer 1,2-dichlorohexafluorocyclobutane (F6, also known as 2N) does cause amnesia and seizures. These occur at 0.48 and 1.3 times, respectively, the concentrations that are predicted from its lipid solubility to cause immobility. The molecular and cellular basis of these effects is not known. The ionotropic gamma-aminobutyric acid type A (GABAA) receptor is modulated strongly by anesthetics, and it plays an important role in many seizure models. Also, the hippocampus is a structure central to the formation of memory and is susceptible to seizure generation. The authors therefore investigated the effect of F6 on GABAA receptor- mediated inhibition in hippocampal neurons. Transverse hippocampal slices were prepared from young (12- to 21-day-old) Sprague-Dawley rats. Inhibitory postsynaptic currents were recorded from hippocampal CA1 pyramidal cells in the presence of ionotropic glutamate receptor antagonists. F6 was applied with the bath solution. The concentration of F6 achieved during the experiment at the location of synaptic inhibition was derived using a diffusion model. At tissue concentrations of up to 75 microm (approximately 5 x predicted...Continue Reading

References

Aug 1, 1971·British Journal of Anaesthesia·T A JoasE I Eger
Dec 1, 1994·Anesthesia and Analgesia·D E Raines, K W Miller
Dec 1, 1994·Anesthesia and Analgesia·D D KoblinP Ionescu
Jan 7, 1993·Nature·T V Bliss, G L Collingridge
Jan 1, 1996·Hippocampus·T F Freund, G Buzsáki
Mar 12, 1998·Anesthesia and Analgesia·J SonnerE I Eger
Jul 4, 1998·Brain Research. Brain Research Reviews·J P ChangeuxM Zoli
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Jul 24, 2001·Anesthesiology·W SimonG Rammes
Apr 8, 2003·Nature Neuroscience·Alexey SemyanovDimitri M Kullmann

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