title: Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats.
abstract: Sleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well-known energy booster in cellular energy homeostasis. Oral Cr-monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high-energy molecules and sleep-wake behaviour is unclear. Here, we examined the sleep-wake behaviour and brain energy metabolism before and after 4-week-long oral administration of CS in the rat. CS decreased total sleep time and non-rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation-induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep-related disorders.
authors.affiliation: Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System and Harvard Medical School, West Roxbury, MA, USA.|Institute of Movement and Neurosciences, German Sport University Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Dworak
authors.affiliation: Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System and Harvard Medical School, West Roxbury, MA, USA.|Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, South Korea.
authors.forename: Tae
authors.initials: T
authors.lastname: Kim
authors.affiliation: Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System and Harvard Medical School, West Roxbury, MA, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mccarley
authors.affiliation: Laboratory of Neuroscience, Department of Psychiatry, VA Boston Healthcare System and Harvard Medical School, West Roxbury, MA, USA.
authors.forename: Radhika
authors.initials: R
authors.lastname: Basheer
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003401:Creatine / Q000008:administration & dosage / Q000494:pharmacology*; D004569:Electroencephalography; D004734:Energy Metabolism / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects*; D008297:Male; D017551:Microdialysis; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects* / Q000502:physiology*; D012892:Sleep Deprivation / Q000188:drug therapy / Q000378:metabolism; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology
chemical_list: D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D000241:Adenosine; D003401:Creatine
keywords: creatine; energy metabolism; sleep deprivation; sleep homeostasis