title: Isoflurane causes concentration-dependent inhibition of medullary raphé 5-HT neurons in situ.
abstract: BACKGROUND
  Anesthetics have a profound influence on a myriad of autonomic processes. Mechanisms of general anesthesia, and how these mechanisms give rise to the multifaceted state of anesthesia, are largely unknown. The ascending and descending serotonin (5-HT) networks are key modulators of autonomic pathways, and are critically involved in homeostatic reflexes across the motor, somatosensory, limbic and autonomic systems. These 5-HT networks are thought to contribute to anesthetic effects, but how anesthetics affect 5-HT neuron function remains a pertinent question. We hypothesized that the volatile anesthetic isoflurane inhibits action potential discharge of medullary raphé 5-HT neurons.
  
  
  METHODS
  We conducted extracellular recordings on individual neurons in the medullary raphé region of the unanesthetized in situ perfused brainstem preparation to determine how exposure to isoflurane affects 5-HT neurons. We examined changes in 5-HT neuron baseline firing in response to treatment with either 1, 1.5, or 2% isoflurane. We measured isoflurane concentrations by gas chromatography-mass spectrometry (GC-MS) analysis.
  
  
  RESULTS
  Exposure to isoflurane inhibited action potential discharge in raphé 5-HT neurons. We document a concentration-dependent inhibition over a range of concentrations approximating isoflurane MAC (minimum alveolar concentration required for surgical anesthesia). Delivered concentrations of isoflurane were confirmed using GC-MS analysis.
  
  
  CONCLUSIONS
  These findings illustrate that halogenated anesthetics greatly affect 5-HT neuron firing and suggest 5-HT neuron contributions to mechanisms of general anesthesia.
authors.affiliation: Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska, Fairbanks, AK 99775, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Johansen
authors.affiliation: Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska, Fairbanks, AK 99775, USA.
authors.forename: K E
authors.initials: KE
authors.lastname: Iceman
authors.affiliation: Department of Chemistry and Biochemistry, University of Alaska, Fairbanks, AK 99775, USA.
authors.forename: C R
authors.initials: CR
authors.lastname: Iceman
authors.affiliation: Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska, Fairbanks, AK 99775, USA.
authors.forename: B E
authors.initials: BE
authors.lastname: Taylor
authors.affiliation: Institute of Arctic Biology, Department of Biology and Wildlife, University of Alaska, Fairbanks, AK 99775, USA. Electronic address: mbharris@alaska.edu.
authors.forename: M B
authors.initials: MB
authors.lastname: Harris
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008401:Gas Chromatography-Mass Spectrometry; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008839:Microelectrodes; D009433:Neural Inhibition / Q000187:drug effects* / Q000502:physiology; D011903:Raphe Nuclei / Q000187:drug effects* / Q000502:physiology; D017207:Rats, Sprague-Dawley; D059326:Serotonergic Neurons / Q000187:drug effects* / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D018685:Anesthetics, Inhalation; D007530:Isoflurane
keywords: Anesthesia; Autonomic; Isoflurane; Raphé; Serotonin