The wake-promoting effects of hypocretin-1 are attenuated in old rats.
Disruption of sleep is a frequent complaint among elderly humans and is also evident in aged laboratory rodents. The neurobiological bases of age-related sleep/wake disruption are unknown. Given the critical role of the hypocretins in sleep/wake regulation, we sought to determine whether the wake-promoting effect of hypocretin changes with age in Wistar rats, a strain in which age-related changes in both sleep and hypocretin signaling have been reported. Intracerebroventricular infusions of hypocretin-1 (10 and 30 μg) significantly increased wake time relative to vehicle in both young (3 mos) and old (25 mos) Wistar rats. However, the magnitude and duration of the wake-promoting effects were attenuated with age. An increase of parameters associated with homeostatic sleep recovery after sleep deprivation, including non-rapid eye movement (NR) sleep time, NR delta power, the ratio of NR to rapid eye movement (REM) sleep, and NR consolidation, occurred subsequent to Hcrt-induced waking in young but not old rats. ICV infusions of hypocretin-2 (10 and 30 μg) produced fewer effects in both young and old rats. These data demonstrate that activation of a major sleep/wake regulatory pathway is attenuated in old rats.
Biosciences Division, SRI International, CA 94025, USA. stephen.morairty@sri.com
Stephen R
SR
Morairty
Jonathan
J
Wisor
Kristy
K
Silveira
William
W
Sinko
Thomas S
TS
Kilduff
D000375:Aging / Q000502:physiology*; D000818:Animals; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009479:Neuropeptides / Q000378:metabolism / Q000502:physiology*; D000068797:Orexins; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013566:Sympathomimetics / Q000494:pharmacology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D013566:Sympathomimetics