title: Melatonin promotes sleep in three species of diurnal nonhuman primates.
abstract: Nocturnal melatonin secretion is concurrent with consolidated sleep episodes in diurnal mammals and physiological melatonin levels can promote sleep onset in humans and in pigtail macaques. In order to further investigate the effects of melatonin treatment on sleep parameters in diurnal nonhuman primates, three macaque species have been studied: Macaca nemestrina, Macaca fascicularis, and Macaca mulatta. Sleep was assessed using continuous actigraphic recording of motor activity in animals maintained under 12:12-h light/dark cycle. Oral doses of melatonin (5-320 microg/kg) were administered 2 h before lights-off time, with 5- and 10-microg/kg doses resulting in physiological circulating melatonin levels (31-95 pg/ml). The effects of melatonin administration were similar in three species studied and included significantly earlier sleep onset time and longer sleep period time, with no difference in time of awakening, following administration of both physiological (5-10 microg/kg) and pharmacological (20-320 microg/kg) doses. While low melatonin doses (5-20 microg/kg) did not significantly affect nighttime sleep efficiency, higher pharmacological doses reduced sleep efficiency and increased sleep fragmentation at night, and reduced spontaneous daytime locomotor activity. Daily administration of a 5-microg/kg dose for 4 weeks or gradually escalating melatonin doses (5-320 microg/kg over a 3-week period) did not result in the development of tolerance or sensitization to the effect of melatonin on sleep initiation or sleep period. These data affirm that sleep-promoting effects of melatonin observed in humans are also typical for diurnal primates. They also suggest that physiological and pharmacological melatonin levels might produce different effects on sleep efficiency and that nonhuman primates can serve as adequate animal model for studying the mechanisms of melatonin's action on sleep and performance.
authors.affiliation: Massachusetts Institute of Technology, Cambridge, MA 02139, USA. zhdanova@cajal-1.bu.edu
authors.forename: Irina V
authors.initials: IV
authors.lastname: Zhdanova
authors.forename: David A
authors.initials: DA
authors.lastname: Geiger
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Schwagerl
authors.forename: Ojingwa U
authors.initials: OU
authors.lastname: Leclair
authors.forename: Ronald
authors.initials: R
authors.lastname: Killiany
authors.forename: Judy A
authors.initials: JA
authors.lastname: Taylor
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Rosene
authors.forename: Mark B
authors.initials: MB
authors.lastname: Moss
authors.forename: Bertha K
authors.initials: BK
authors.lastname: Madras
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002940:Circadian Rhythm / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D017286:Polysomnography; D012890:Sleep / Q000187:drug effects*; D013045:Species Specificity
chemical_list: D008550:Melatonin