The diurnal rhythm of adenosine levels in the basal forebrain of young and old rats.
There are significant decrements in sleep with age. These include fragmentation of sleep, increased wake time, decrease in the length of sleep bouts, decrease in the amplitude of the diurnal rhythm of sleep, decrease in rapid eye movement sleep and a profound decrease in electroencephalogram Delta power (0.3-4 Hz). Old rats also have less sleep in response to 12 h-prolonged wakefulness (W) indicating a reduction in sleep drive with age. The mechanism contributing to the decline in sleep with aging is not known but cannot be attributed to loss of neurons implicated in sleep since the numbers of neurons in the ventral lateral preoptic area, a region implicated in generating sleep, is similar between young (3.5 months) and old (21.5 months) rats. One possibility for the reduced sleep drive with age is that sleep-wake active neurons may be stimulated less as a result of a decline in endogenous sleep factors. Here, we test this hypothesis by focusing on the purine, adenosine (AD), one such sleep factor that increases after prolonged W. In experiment 1, microdialysis measurements of AD in the basal forebrain at 1 h intervals reveal that old (21.5 months) rats have more extracellular levels of AD compared with young rats across the 24 h diurnal cycle. In experiment 2, old rats kept awake for 6 h (first half of lights-on period) accumulated more AD compared with young rats. If old rats have more AD then why do they sleep less? To investigate whether changes in sensitivity of the AD receptor contribute to the decline in sleep, experiments 3 and 4 determined that for the same concentration of AD or the AD receptor 1 agonist, cyclohexyladenosine, old rats have less sleep compared with young rats. We conclude that even though old rats have more AD, a reduction in the sensitivity of the AD receptor to the ligand does not transduce the AD signal at the same strength as in young rats and may be a contributing factor to the decline in sleep drive in the elderly.
Murillo-Rodriguez
E
E
Department of Neurology, West Roxbury VA Medical Center and Harvard Medical School, Building 3, Room 2C109, 1400 VFW Parkway, West Roxbury, MA 02132, USA.
Blanco-Centurion
C
C
Gerashchenko
D
D
Salin-Pascual
R J
RJ
Shiromani
P J
PJ
D000241:Adenosine / Q000032:analysis / Q000378:metabolism*; D000375:Aging; D000818:Animals; D001923:Brain Chemistry / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D002940:Circadian Rhythm / Q000502:physiology*; D004569:Electroencephalography; D017551:Microdialysis; D016548:Prosencephalon / Q000378:metabolism; D051381:Rats; D018047:Receptors, Purinergic P1; D012890:Sleep / Q000502:physiology*
D018047:Receptors, Purinergic P1; D000241:Adenosine