title: The anesthetic urethane blocks excitatory amino acid responses but not GABA responses in isolated frog spinal cords.
abstract: OBJECTIVE
  The anesthetic urethane is commonly used in physiological experiments. We tested urethane's actions on GABA receptors on the primary afferents in the spinal cord, which are one of the few areas in the adult central nervous system (CNS) that are depolarized by GABA, and on ligand-gated excitatory amino acid (EAA) receptors located on motoneurons. Both receptor types are critically important during anesthetic immobilization.
  
  
  METHODS
  We used the isolated hemisected spinal cord of the frog in a sucrose gap chamber to record glutamate-, N-methyl-D-aspartate (NMDA)-, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-, kainate-, and gamma-aminobutyric acid (GABA)-induced depolarizations of the dorsal root (DR) and ventral root (VR). DR potentials (DRPs) and VR potentials (VRPs) evoked by single supramaximal afferent stimuli were also studied. Urethane (10-80 mM) was applied for 10-30 min.
  
  
  RESULTS
  Urethane depressed EAA responses on the motoneurons in a dose-dependent manner. At a clinical anesthetic concentration (10 mM), EAA-induced depolarizations were reduced by 8.1 ± 2.2 % (n = 7, P = 0.025), but increasing the concentration to 40 mM revealed a larger, 24.7 ± 3 % (n = 53, P = 0.0001) depressing effect of urethane on all EAA responses in the motoneurons. However, GABA and K(+) responses recorded in the DR were not altered by the presence of 10 or 40 mM urethane. Evoked DRPs and VRPs were reduced by urethane and spontaneous DR and VR potentials were suppressed by 10 or blocked by 40 mM urethane.
  
  
  CONCLUSIONS
  Urethane appears to be selective for EAA-, sparing GABA responses at a clinical anesthetic concentration. Only a 10 % reduction of EAA activity seems to be necessary to induce anesthesia.
authors.affiliation: VA Medical Center and Department of Neurology and Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33101, USA. nelsondalo@yahoo.com
authors.forename: Nelson L
authors.initials: NL
authors.lastname: Daló
authors.forename: John C
authors.initials: JC
authors.lastname: Hackman
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D066298:In Vitro Techniques; D009046:Motor Neurons / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D011894:Rana pipiens; D018091:Receptors, AMPA / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D013119:Spinal Cord Injuries; D013126:Spinal Nerve Roots / Q000187:drug effects; D014520:Urethane / Q000494:pharmacology*
chemical_list: D018686:Anesthetics, Intravenous; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D014520:Urethane; D011188:Potassium