Involvement of adenosine A2A receptor in sleep promotion.

We examined the sleep-modulatory effects of four adenosine agonists, namely, (1) 2-(4-(2-carboxyethyl)phenylethylamino)adenosine-5'-N-ethylcarbo xamideadenosine (CGS21680), a highly selective adenosine A2A receptor agonist; (2) 2-(4-(2-(2-aminoethylaminocarbonyl)ethyl)phenylethylamino)-5 '-N-ethylcarboxamidoadenosine (APEC), a selective adenosine A2A receptor agonist; (3) 5'-N-ethylcarboxamidoadenosine (NECA), a nonselective adenosine A1/A2 receptor agonist, and (4) N6-cyclopentyladenosine (CPA), a selective adenosine A1 receptor agonist. Each agonist was administered in the subarachnoid space underlying the rostral basal forebrain of rats through chronically implanted cannulae at the rate of 0.02, 0.2, 2.0, 12.0, or 20.0 pmol/min over a 6-h period starting from 2300 h, which period is the active phase of the animals. CGS21680, APEC, and NECA produced significant increases in the total amounts of non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep after at least one dose within the range of administration rates. CPA did not produce any significant increase in the total amount of either type of sleep at any of the above administration rates, but instead suppressed REM sleep at the administration rates of 12.0 and 20.0 pmol/min. These results indicate that the activities of adenosine A2A receptors are crucially involved in the promotion of sleep.