title: Membrane fluidity does not explain how solvents act on the middle-ear reflex.
abstract: Some volatile aromatic solvents have similar or opposite effects to anesthetics in the central nervous system. Like for anesthetics, the mechanisms of action involved are currently the subject of debate. This paper presents an in vivo study to determine whether direct binding or effects on membrane fluidity best explain how solvents counterbalance anesthesia's depression of the middle-ear reflex (MER). Rats were anesthetized with a mixture of ketamine and xylazine while also exposed to solvent vapors (toluene, ethylbenzene, or one of the three xylene isomers) and the amplitude of their MER was monitored. The depth of anesthesia was standardized based on the magnitude of the contraction of the muscles involved in the MER, determined by measuring cubic distortion product oto-acoustic emissions (DPOAEs) while triggering the bilateral reflex with contralateral acoustic stimulation. The effects of the aromatic solvents were quantified based on variations in the amplitude of the DPOAEs. The amplitude of the alteration to the MER measured in anesthetized rats did not correlate with solvent lipophilocity (as indicated by logKow values). Results obtained with the three xylene isomers indicated that the positions of two methyl groups around the benzene ring played a determinant role in solvent/neuronal cell interaction. Additionally, Solid-state Nuclear Magnetic Resonance (NMR) spectra for brain microsomes confirmed that brain lipid fluidity was unaffected by solvent exposure, even after three days (6h/day) at an extremely high concentration (3000ppm). Therefore, aromatic solvents appear to act directly on the neuroreceptors involved in the acoustic reflex circuit, rather than on membrane fluidity. The affinity of this interaction is determined by stereospecific parameters rather than lipophilocity.
authors: Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France.
authors: Ludivine
authors: L
authors: Wathier
authors: Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France.
authors: Thomas
authors: T
authors: Venet
authors: Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France.
authors: Aurélie
authors: A
authors: Thomas
authors: Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France.
authors: Hervé
authors: H
authors: Nunge
authors: Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France.
authors: Elodie
authors: E
authors: Bonfanti
authors: Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France.
authors: Frédéric
authors: F
authors: Cosnier
authors: Service O.R.L. et Chirurgie Cervico-faciale CHU-Hôpital Central, Nancy, F-54000, France.
authors: Cécile
authors: C
authors: Parietti-Winkler
authors: Institut National de Recherche et de Sécurité, Rue du Morvan, F-54519 Vandoeuvre-les-Nancy, France. Electronic address: pierre.campo@inrs.fr.
authors: Pierre
authors: P
authors: Campo
authors: Université de Lorraine, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France; CNRS, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France.
authors: Pascale
authors: P
authors: Tsan
authors: Université de Lorraine, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France; CNRS, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France.
authors: Sabine
authors: S
authors: Bouguet-Bonnet
authors: Université de Lorraine, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France; CNRS, CRM2, UMR 7036, Vandoeuvre-les-Nancy, F-54506, France.
authors: Axel
authors: A
authors: Gansmüller
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D001921:Brain / Q000378:metabolism; D004432:Ear, Middle / Q000187:drug effects / Q000502:physiology*; D007839:Functional Laterality / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008560:Membrane Fluidity / Q000187:drug effects* / Q000502:physiology; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D051381:Rats; D012022:Reflex, Acoustic / Q000187:drug effects* / Q000502:physiology; D012997:Solvents / Q000378:metabolism / Q000494:pharmacology*; D014050:Toluene / Q000494:pharmacology; D014316:Tritium / Q000493:pharmacokinetics
chemical_list: D012997:Solvents; D014316:Tritium; D014050:Toluene
keywords: Anesthetics; Membrane fluidity; NMR; Solvent; Stapedial reflex; Stereospecificity