Adenosine and behavioral state control: adenosine increases c-Fos protein and AP1 binding in basal forebrain of rats

In several brain areas, extracellular adenosine (AD) levels are higher duri ng waking than sleep and during prolonged wakefulness AD levels in the basa l forebrain increase progressively. Similarly, c-Fos levels in several brai n areas are higher during waking than sleep and remain elevated during prol onged wakefulness. In the present study, we investigated the effect of extr acellular AD levels on c-Fos protein and activator protein-1 (AP1) binding in the basal forebrain of rats. Increased levels of extracellular AD were i nduced either by keeping the animals awake, or by local perfusion of AD int o the basal forebrain. During prolonged wakefulness extracellular AD concen tration was monitored using in vivo microdialysis. The effect of AD perfusi on on the behavioral states was recorded using polysomnography. At the end of the perfusion period the basal forebrain tissue was analyzed for the lev els of c-Fos protein and AP1 binding. In vivo microdialysis measurements sh owed an increase in AD levels with prolonged wakefulness. Unilateral perfus ion of AD (300 mu M) increased non-REM sleep and delta power (0.5 to 4 Hz) when compared to rats perfused with artificial CSF. The levels of c-Fos pro tein and the API DNA binding were high in the basal forebrain of both sleep -deprived animals and in animals perfused with AD. The results suggest that AD might mediate, at least in part, the long term effects of sleep depriva tion by inducing c-Fos protein and subsequent AP1 binding. (C) 1999 Elsevie r Science B.V. All rights reserved.