Decoupling of sleepiness from sleep time and intensity during chronic sleep restriction: evidence for a role of the adenosine system.
OBJECTIVE
Sleep responses to chronic sleep restriction (CSR) might be very different from those observed after short-term total sleep deprivation. For example, after sleep restriction continues for several consecutive days, animals no longer express compensatory increases in daily sleep time and sleep intensity. However, it is unknown if these allostatic, or adaptive, sleep responses to CSR are paralleled by behavioral and neurochemical measures of sleepiness.


METHODS
This study was designed to investigate CSR-induced changes in (1) sleep time and intensity as a measure of electrophysiological sleepiness, (2) sleep latency as a measure of behavioral sleepiness, and (3) brain adenosine A1 (A1R) and A2a receptor (A2aR) mRNA levels as a putative neurochemical correlate of sleepiness.


METHODS
Male Sprague-Dawley rats


METHODS
A 5-day sleep restriction (SR) protocol consisting of 18-h sleep deprivation and 6-h sleep opportunity each day.


RESULTS
Unlike the first SR day, rats did not sleep longer or deeper on days 2 through 5, even though they exhibited significant elevations of behavioral sleepiness throughout all 5 SR days. For all SR days and recovery day 1, A1R mRNA in the basal forebrain was maintained at elevated levels, whereas A2aR mRNA in the frontal cortex was maintained at reduced levels.


CONCLUSIONS
CSR LEADS TO A DECOUPLING OF SLEEPINESS FROM SLEEP TIME AND SLEEP INTENSITY, SUGGESTING THAT THERE ARE AT LEAST TWO DIFFERENT SLEEP REGULATORY SYSTEMS: one mediating sleepiness (homeostatic) and the other mediating sleep time/intensity (allostatic). The time course of changes observed in adenosine receptor mRNA levels suggests that the basal forebrain and cortical adenosine system might mediate sleepiness rather than sleep time or intensity.
VA Boston Healthcare System, Research Service and Harvard Medical School, Department of Psychiatry, Brockton, MA 02301-5596, USA. youngsoo_kim@hms.harvard.edu
Youngsoo
Y
Kim
Yunren
Y
Bolortuya
Lichao
L
Chen
Radhika
R
Basheer
Robert W
RW
McCarley
Robert E
RE
Strecker
D000818:Animals; D004569:Electroencephalography; D008297:Male; D008780:Methyltransferases; D009687:Nuclear Proteins; D016548:Prosencephalon / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D043682:Receptor, Adenosine A1 / Q000032:analysis / Q000502:physiology; D043683:Receptors, Adenosine A2 / Q000032:analysis / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000032:analysis* / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000503:physiopathology*; D014851:Wakefulness / Q000502:physiology*
D009687:Nuclear Proteins; D043682:Receptor, Adenosine A1; D043683:Receptors, Adenosine A2; D018047:Receptors, Purinergic P1; C549212:EMG1 protein, human; D008780:Methyltransferases