Microdialysis elevation of adenosine in the basal forebrain produces vigilance impairments in the rat psychomotor vigilance task.
OBJECTIVE
The inhibitory neuromodulator adenosine has been proposed as a homeostatic sleep factor that acts potently in the basal forebrain (BF) to increase sleepiness. Here 300 microM of adenosine was dialyzed in the BF of rats, and the effect on vigilance was determined in the rat Psychomotor Vigilance Task (rPVT).


METHODS
Rats experienced all experimental conditions in a repeated-measures, cross-over design.


METHODS
Twelve young adult male Fischer-Norway rats.


METHODS
Sustained attention performance in the rPVT was evaluated following 2 hours of bilateral microdialysis perfusion of vehicle, adenosine (300 microM), or codialysis of 300 microM of adenosine with the A1 receptor antagonist 8-cyclopentyltheophylline.


RESULTS
During rPVT performance, response latencies and performance lapses increased significantly after adenosine dialysis when compared with baseline (no dialysis) or vehicle dialysis sessions. The codialysis of 8-cyclopentyltheophylline with adenosine completely blocked the effects produced by adenosine alone, resulting in performance equivalent to that of the vehicle sessions.


CONCLUSIONS
Pharmacologic elevation of BF adenosine in rats produced vigilance impairments resembling the effect of sleep deprivation on vigilance performance in both man and rats. This effect of exogenous adenosine was completely blocked by codialysis with an adenosine A1 receptor antagonist. The results are consistent with the hypothesis that sleep loss induces elevations of BF adenosine that, acting via A1 receptors, lead to increased sleepiness and impaired vigilance.
VA Boston Healthcare System, Brockton, MA, USA. michael_christie@hms.harvard.edu
Michael A
MA
Christie
Yunren
Y
Bolortuya
Li Chao
LC
Chen
James T
JT
McKenna
Robert W
RW
McCarley
Robert E
RE
Strecker
D000241:Adenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D001143:Arousal / Q000187:drug effects*; D001288:Attention / Q000187:drug effects*; D017551:Microdialysis; D016548:Prosencephalon / Q000187:drug effects*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D011930:Reaction Time / Q000187:drug effects; D012890:Sleep / Q000187:drug effects*; D013806:Theophylline / Q000031:analogs & derivatives
C055488:8-cyclopropyltheophylline; D013806:Theophylline; D000241:Adenosine