D1 receptor agonist improves sleep-wake parameters in experimental parkinsonism

Neurobiol Dis. 2014 Mar:63:20-4. doi: 10.1016/j.nbd.2013.10.029. Epub 2013 Nov 6.

Abstract

Both excessive daytime sleepiness (EDS) and rapid eye movement (REM) sleep deregulation are part of Parkinson's disease (PD) non-motor symptoms and may complicate dopamine replacement therapy. We report here that dopamine agonists act differentially on sleep architecture in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine macaque monkey. Continuous sleep and wake electroencephalographic monitoring revealed no effect of the selective dopamine D2 receptor agonist quinpirole on EDS, whereas the selective dopamine D1 receptor agonist SKF38393 efficiently alleviated EDS and restored REM sleep to baseline values. The present results question the relevance of abandoning D1 receptor agonist treatment in PD as it might actually improve sleep-related disorders.

Keywords: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; EDS; EEG; EMG; EOG; Excessive daytime sleepiness; MPTP; Non-human primate; PD; Parkinson's disease; REM; Rapid eye movement sleep; Sleep disorders; electroencephalogram; electromyogram; electrooculogram; excessive daytime sleepiness; rapid eye movement.

MeSH terms

  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / therapeutic use
  • Analysis of Variance
  • Animals
  • Disease Models, Animal
  • Dopamine Agonists / therapeutic use*
  • Dose-Response Relationship, Drug
  • Electrocardiography
  • Electroencephalography
  • Electromyography
  • Female
  • Levodopa / therapeutic use
  • Macaca fascicularis
  • Macaca mulatta
  • Parkinsonian Disorders / complications*
  • Parkinsonian Disorders / drug therapy
  • Quinpirole / therapeutic use
  • Sleep / drug effects
  • Sleep Disorders, Circadian Rhythm / drug therapy*
  • Sleep Disorders, Circadian Rhythm / etiology*
  • Telemetry
  • Time Factors
  • Wakefulness / drug effects

Substances

  • Dopamine Agonists
  • Quinpirole
  • Levodopa
  • 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine