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How to keep the brain awake? The complex molecular pharmacogenetics of wake promotion.

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  • 2009-02-06
Published in:
  • Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - 2009
Animals
Benzhydryl Compounds
Brain
Central Nervous System Stimulants
Dextroamphetamine
Dose-Response Relationship, Drug
Electroencephalography
Electromyography
Gene Expression Regulation
Genotype
Male
Mice
Mice, Inbred Strains
Modafinil
Nerve Tissue Proteins
Pharmacogenetics
Phenylalanine
Proto-Oncogene Proteins c-fos
Sleep
Species Specificity
Spectrum Analysis
Statistics as Topic
Time Factors
Wakefulness
English Wake-promoting drugs are widely used to treat excessive daytime sleepiness. The neuronal pathways involved in wake promotion are multiple and often not well characterized. We tested d-amphetamine, modafinil, and YKP10A, a novel wake-promoting compound, in three inbred strains of mice. The wake duration induced by YKP10A and d-amphetamine depended similarly on genotype, whereas opposite strain differences were observed after modafinil. Electroencephalogram (EEG) analysis during drug-induced wakefulness revealed a transient approximately 2 Hz slowing of theta oscillations and an increase in beta-2 (20-35 Hz) activity only after YKP10A. Gamma activity (35-60 Hz) was induced by all drugs in a drug- and genotype-dependent manner. Brain transcriptome and clustering analyses indicated that the three drugs have both common and specific molecular signatures. The correlation between specific EEG and gene-expression signatures suggests that the neuronal pathways activated to stay awake vary among drugs and genetic background.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/265107
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