Role of adenosine in sleep in rats

The effects on sleep of N6-L-(phenylisopropyl) adenosine, cyclohexyladenosine and adenosine-5'-ethylcarboxamide were studied in rats. Also, the effects on sleep of deoxycoformycin, a potent inhibitor of adenosine deaminase, and adenosine were examined. In addition, we determined the effects of 48 h of REM sleep deprivation on adenosine (A1) receptors in specific brain structures. N6-L-(phenylisopropyl) adenosine and cyclohexyl-adenosine increased deep slow wave sleep and REM sleep whereas adenosine-5'-ethylcarboxamide increased only deep slow-wave sleep. At the dose of 0.9 mumol/kg all three adenosine analogs suppressed REM sleep and except for adenosine-5-ethylcarboxamide, were without an effect on deep slow-wave sleep. In accordance, administration of deoxycoformycin increased REM and deep slow-wave sleep. Intracerebroventricular administration of 1, 10 and 100 nmoles of adenosine to rats decreased waking, increased deep slow-wave sleep and increased total sleep. In addition, REM sleep deprivation significantly increased the number of A1 receptors (Bmax) in cerebral cortex and corpus striatum which correlates with the increased pressure for REM sleep and the onset of REM sleep rebound. When these data are taken together, they indicate a role for adenosine in the regulation of sleep and, in contrast to barbiturate and benzodiazepine hypnotics, increase in behaviorally deep and REM sleep.