title: Norepinephrine infusion into nucleus basalis elicits microarousal in desflurane-anesthetized rats.
abstract: BACKGROUND
  The nucleus basalis of Meynert of the basal forebrain has been implicated in the regulation of the state of consciousness across normal sleep-wake cycles. Its role in the modulation of general anesthesia was investigated.
  
  
  METHODS
  Rats were chronically implanted with bilateral infusion cannulae in the nucleus basalis of Meynert and epidural electrodes to record the electroencephalogram in frontal and visual cortices. Animals were anesthetized with desflurane at a concentration required for the loss of righting reflex (4.6 ± 0.5%). Norepinephrine (17.8 nmol) or artificial cerebrospinal fluid was infused at 0.2 μl/min (1 μl total). Behavioral response to infusion was measured by scoring the orofacial, limb, and head movements, and postural changes.
  
  
  RESULTS
  Behavioral responses were higher after norepinephrine (2.1 ± 1) than artificial cerebrospinal fluid (0.63 ± 0.8) infusion (P < 0.01, Student t test). Responses were brief (1-2 min), repetitive, and more frequent after norepinephrine infusion (P < 0.0001, chi-square test). Electroencephalogram delta power decreased after norepinephrine in frontal (70 ± 7%) but not in visual cortex (P < 0.05, Student t test). Simultaneously, electroencephalogram cross-approximate entropy between frontal and visual cortices increased from 3.17 ± 0.56 to 3.85 ± 0.29 after norepinephrine infusion (P < 0.01, Student t test). Behavioral activation was predictable by the decrease in frontal delta power (logistic regression, P < 0.05).
  
  
  CONCLUSIONS
  Norepinephrine infusion into the nucleus basalis of Meynert can modulate anesthetic depth presumably by ascending activation of the cortex. The transient nature of the responses suggests a similarity with microarousals normally observed during natural sleep, and may imply a mechanism for transient awareness under light anesthesia.
authors.affiliation: Department of Biophysics, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Siveshigan
authors.initials: S
authors.lastname: Pillay
authors.forename: Jeannette A
authors.initials: JA
authors.lastname: Vizuete
authors.forename: J Bruce
authors.initials: JB
authors.lastname: McCallum
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Hudetz
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage* / Q000494:pharmacology*; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D020532:Basal Nucleus of Meynert / Q000502:physiology*; D001522:Behavior, Animal / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects; D003627:Data Interpretation, Statistical; D000077335:Desflurane; D004569:Electroencephalography / Q000187:drug effects; D019277:Entropy; D007267:Injections; D007530:Isoflurane / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage* / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D057897:Reflex, Righting; D012890:Sleep / Q000187:drug effects; D014793:Visual Cortex / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D018685:Anesthetics, Inhalation; D000077335:Desflurane; D007530:Isoflurane; D009638:Norepinephrine