Norepinephrine-deficient mice exhibit normal sleep-wake states but have shorter sleep latency after mild stress and low doses of amphetamine.
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.
Hunsley
Melissa S
MS
Howard Hughes Medical Institute, University of Washington, Seattle 98195-7370, USA. mh8@u.washington.edu
Palmiter
Richard D
RD
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*
D015259:Dopamine Agents; D000661:Amphetamine; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine