Adenosine: A mediator of the sleep-inducing effects of prolonged wakefulness

Tarja Porkka-Heiskanen, Robert E. Strecker, Mahesh Thakkar, Alvhild A. Bjørkum, Robert W. Greene, Robert W. McCarley

Research output: Contribution to journalArticlepeer-review

444 Scopus citations


Both subjective and electroencephalographic arousal diminish as a function of the duration of prior wakefulness. Data reported here suggest that the major criteria for a neural sleep factor mediating the somnogenic effects of prolonged wakefulness are satisfied by adenosine, a neuromodulator whose extracellular concentration increases with brain metabolism and which, in vitro, inhibits basal forebrain cholinergic neurons. In vivo microdialysis measurements in freely behaving cats showed that adenosine extracellular concentrations in the basal forebrain cholinergic region increased during spontaneous wakefulness as contrasted with slow wave sleep; exhibited progressive increases during sustained, prolonged wakefulness; and declined slowly during recovery sleep. Furthermore, the sleep-wakefulness profile occurring after prolonged wakefulness was mimicked by increased extracellular adenosine induced by microdialysis perfusion of an adenosine transport inhibitor in the cholinergic basal forebrain but not by perfusion in a control noncholinergic region.

Original languageEnglish (US)
Pages (from-to)1265-1267
Number of pages3
Issue number5316
StatePublished - May 23 1997

ASJC Scopus subject areas

  • General


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