title: Norepinephrine-deficient mice exhibit normal sleep-wake states but have shorter sleep latency after mild stress and low doses of amphetamine.
abstract: OBJECTIVE
  Mice lacking the ability to make norepinephrine (NE) were used to investigate how NE may be involved in regulating sleep and sleep latency under normal conditions and as a response to mild stress or varying doses of amphetamine.
  
  
  METHODS
  Sleep latency was measured in NE-deficient and control mice after behavioral interventions and after 3 low doses of amphetamine. Sleep-wake states were measured using electroencephalography and electromyography for the first 6 hours after lights-on under baseline conditions and after an injection of saline. The first 6 hours after lights-off were also measured under baseline conditions.
  
  
  METHODS
  N/A.
  
  
  METHODS
  Mice lacking the dopamine beta-hydroxylase gene (Dbh -/-), which is required for NE synthesis, and their littermate controls were used.
  
  
  METHODS
  N/A.
  
  
  RESULTS
  As measured behaviorally and with electroencephalography, sleep latency was significantly shorter in the NE-deficient mice after cage changing, saline injection, and 3 different doses of amphetamine. There were no differences between the 2 groups in any sleep parameters under baseline conditions or after saline injection during the day or night.
  
  
  CONCLUSIONS
  The NE-deficient mice showed a significantly shorter latency to sleep under many different conditions, measured both behaviorally and with electroencephalography. These data suggest that NE is wake promoting during the period of time between a mildly stressful event or a low dose of amphetamine and sleep onset. The NE-deficient mice did not show deficits in wake or increases in rapid eye movement sleep, as predicted from current models of the involvement of NE in the regulation of these 2 states.
authors.affiliation: Howard Hughes Medical Institute, University of Washington, Seattle 98195-7370, USA. mh8@u.washington.edu
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Hunsley
authors.forename: Richard D
authors.initials: RD
authors.lastname: Palmiter
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D015259:Dopamine Agents / Q000009:adverse effects*; D004299:Dopamine beta-Hydroxylase / Q000172:deficiency / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000295:instrumentation; D004567:Electrodes, Implanted; D004569:Electroencephalography; D004576:Electromyography; D005133:Eye Movements / Q000187:drug effects; D005260:Female; D005625:Frontal Lobe / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000172:deficiency*; D012895:Sleep, REM / Q000187:drug effects*; D013312:Stress, Physiological / Q000503:physiopathology*; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects*
chemical_list: D015259:Dopamine Agents; D000661:Amphetamine; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine