title: Electrical stimulation of the ventral tegmental area induces reanimation from general anesthesia.
abstract: BACKGROUND
  Methylphenidate or a D1 dopamine receptor agonist induces reanimation (active emergence) from general anesthesia. The authors tested whether electrical stimulation of dopaminergic nuclei also induces reanimation from general anesthesia.
  
  
  METHODS
  In adult rats, a bipolar insulated stainless steel electrode was placed in the ventral tegmental area (VTA, n = 5) or substantia nigra (n = 5). After a minimum 7-day recovery period, the isoflurane dose sufficient to maintain loss of righting was established. Electrical stimulation was initiated and increased in intensity every 3 min to a maximum of 120 µA. If stimulation restored the righting reflex, an additional experiment was performed at least 3 days later during continuous propofol anesthesia. Histological analysis was conducted to identify the location of the electrode tip. In separate experiments, stimulation was performed in the prone position during general anesthesia with isoflurane or propofol, and the electroencephalogram was recorded.
  
  
  RESULTS
  To maintain loss of righting, the dose of isoflurane was 0.9% ± 0.1 vol%, and the target plasma dose of propofol was 4.4 ± 1.1 µg/ml (mean ± SD). In all rats with VTA electrodes, electrical stimulation induced a graded arousal response including righting that increased with current intensity. VTA stimulation induced a shift in electroencephalogram peak power from δ (<4 Hz) to θ (4-8 Hz). In all rats with substantia nigra electrodes, stimulation did not elicit an arousal response or significant electroencephalogram changes.
  
  
  CONCLUSIONS
  Electrical stimulation of the VTA, but not the substantia nigra, induces reanimation during general anesthesia with isoflurane or propofol. These results are consistent with the hypothesis that dopamine release by VTA neurons, but not substantia nigra neurons, induces reanimation from general anesthesia.
authors.affiliation: From the Department of Anaesthesia, Harvard Medical School, Boston, Massachusetts; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts (K.S., C.J.V.D., and N.E.T.); Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital (J.J.C. and J.D.K.); and Department of Anaesthesia, Harvard Medical School; Department of Anesthesia, Critical Care, and Pain Medicine, Massachusetts General Hospital; Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts (E.N.B.).
authors.forename: Ken
authors.initials: K
authors.lastname: Solt
authors.forename: Christa J
authors.initials: CJ
authors.lastname: Van Dort
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Chemali
authors.forename: Norman E
authors.initials: NE
authors.lastname: Taylor
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Kenny
authors.forename: Emery N
authors.initials: EN
authors.lastname: Brown
mesh_terms: D000762:Anesthesia Recovery Period; D000768:Anesthesia, General; D000771:Anesthesia, Intravenous; D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001143:Arousal / Q000187:drug effects; D004298:Dopamine / Q000502:physiology; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D004569:Electroencephalography / Q000187:drug effects; D008297:Male; D015742:Propofol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D018686:Anesthetics, Intravenous; D011954:Receptors, Dopamine; D004298:Dopamine; D015742:Propofol