Norepinephrine-deficient mice exhibit normal sleep-wake states but have shorter sleep latency after mild stress and low doses of amphetamine

Sleep. 2003 Aug 1;26(5):521-6.

Abstract

Study objectives: 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.

Design: 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.

Setting: N/A.

Patients or participants: Mice lacking the dopamine beta-hydroxylase gene (Dbh -/-), which is required for NE synthesis, and their littermate controls were used.

Interventions: N/A.

Measurements and 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.

MeSH terms

  • Amphetamine / administration & dosage
  • Amphetamine / adverse effects*
  • Animals
  • Dopamine Agents / adverse effects*
  • Dopamine beta-Hydroxylase / deficiency
  • Dopamine beta-Hydroxylase / genetics
  • Dose-Response Relationship, Drug
  • Electric Stimulation / instrumentation
  • Electrodes, Implanted
  • Electroencephalography
  • Electromyography
  • Eye Movements / drug effects
  • Female
  • Frontal Lobe / physiology
  • Habituation, Psychophysiologic / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Norepinephrine / deficiency*
  • Sleep, REM / drug effects*
  • Stress, Physiological / physiopathology*
  • Time Factors
  • Wakefulness / drug effects*

Substances

  • Dopamine Agents
  • Amphetamine
  • Dopamine beta-Hydroxylase
  • Norepinephrine