Effect of melatonin on sleep disorders in a monkey model of Parkinson's disease

Sleep Med. 2015 Oct;16(10):1245-51. doi: 10.1016/j.sleep.2015.06.018. Epub 2015 Jul 14.

Abstract

Objectives: To evaluate and compare the effects of melatonin and levodopa (L-dopa) on sleep disorders in a monkey model of Parkinson's disease.

Materials and methods: The daytime and nighttime sleep patterns of four macaques that were rendered parkinsonian by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were recorded using polysomnography in four conditions: at baseline, during the parkinsonian condition; after administration of L-dopa, and after administration of a combination of melatonin with L-dopa.

Results: It was confirmed that MPTP intoxication induces sleep disorders, with sleep episodes during daytime and sleep fragmentation at nighttime. L-dopa treatment significantly reduced the awake time during the night and tended to improve all other sleep parameters, albeit not significantly. In comparison to the parkinsonian condition, combined treatment with melatonin and L-dopa significantly increased total sleep time and sleep efficiency, and reduced the time spent awake during the night in all animals. A significant decrease in sleep latencies was also observed in three out of four animals. Compared with L-dopa alone, combined treatment with melatonin and L-dopa significantly improved all these sleep parameters in two animals. On the other hand, combined treatment had no effect on sleep architecture and daytime sleep.

Conclusion: These data demonstrated, for the first time, objective improvement on sleep parameters of melatonin treatment in MPTP-intoxicated monkeys, showing that melatonin treatment has a real therapeutic potential to treat sleep disturbances in people with Parkinson's disease.

Keywords: MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine); Macaques; Melatonin; Monkeys; Parkinson's disease; Sleep disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparkinson Agents / therapeutic use
  • Central Nervous System Depressants / therapeutic use*
  • Disease Models, Animal
  • Levodopa / therapeutic use
  • Macaca fascicularis
  • Male
  • Melatonin / therapeutic use*
  • Parkinson Disease / complications*
  • Parkinson Disease / drug therapy
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / etiology

Substances

  • Antiparkinson Agents
  • Central Nervous System Depressants
  • Levodopa
  • Melatonin