EXTRACELLULAR ADENOSINE LEVELS IN NEOSTRIATUM AND HIPPOCAMPUS DURING REST AND ACTIVITY PERIODS OF RATS

Adenosine is an inhibitory modulator in the mammalian brain with a pos sible role in sleep regulation, which is mainly indicated by pharmacol ogical studies showing that adenosine or its analogs can induce sedati on and sleep, whereas adenosine antagonists, like caffeine and theophy lline, are potent behavioral and neuronal stimulants. In contrast to t hese pharmacological findings, data on endogenous adenosine in relatio n to sleep and waking are sparse. Therefore, we have now used in vivo microdialysis to investigate the extracellular levels of adenosine in the neostriatum and hippocampus of freely moving rats. Adenosine was m onitored over a time course of 24 h, during which the animals were exp osed to a 12 h day/night rhythm with lights-off from 19.00 to 07.00. I n this lights-off period, i.e. the rats' active period, the maximal le vels of neostriatal and hippocampal extracellular adenosine were highe r than during the lights-on period. In contrast to the neostriatum, ex tracellular levels of hippocampal adenosine tended to increase towards the end of the lights-off period, reaching its maximal level at 07.00 , and decreasing again within the following hour. The changes of hippo campal adenosine levels were related to behavior, since significant in creases in ''sleep-like'' behavior, as well as decreases in overall mo vements and consummatory behavior, were observed when adenosine levels had reached their maxima in the hippocampus; no such relationship was found with respect to the neostriatum. These results are in keeping w ith a role of endogenous adenosine in the regulation of sleep and wake fulness, and point to a specific role of adenosine in the hippocampus. They also raise the possibility that adenosine may be involved in dif ferent behavioral processes dependent on the area of the brain, as wel l as the type of adenosine receptor involved. Finally, given the known evidence for neuroprotective actions of adenosine, its accumulation i n the hippocampus as a function of behavioral activity may serve to pr event or repair the neural degenerative consequences of such activity. It is proposed that adenosine's sleep-promoting effects result from i ts signalling to cease behavioral activity in order to prevent excessi ve activity-related changes, and thus allow other restorative sleep-re lated processes to take over. C) 1996 IBRO. Published by Elsevier Scie nce Ltd.