Melissa S Hunsley1, Richard D Palmiter. 1. Howard Hughes Medical Institute, University of Washington, Seattle 98195-7370, USA. mh8@u.washington.edu
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.
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.