Promotion of sleep mediated by the A(2a)-adenosine receptor and possible involvement of this receptor in the sleep induced by prostaglandin D-2 in rats

A 6-hr continuous infusion of 2-[p-(2-carboxyethyl) phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680), a selective A(2a)-adenosine agonist, into the subarachnoid space underlying the ventral surface region of the rostral basal forebrain, which has been defined as the prostaglandin (PG) D-2-sensitive sleep-promoting zone, at rates of 0.02, 0.2, 2.0, and 12 pmol/min increased slow-wave sleep (SWS) and paradoxical sleep IFS) in a dose-dependent manner up to 183% and 202% of their respective baseline levels. The increments produced by the infusion of CGS21680 at 0.2 and 2.0 pmol/min were totally diminished when the rats had been pretreated with an i,p, injection of (E)-1,3-dipropyl-7-methyl-8-(3,4-dimethoxystyryl)xanthine (KF17837; 30 mg/kg of body weight), a selective A(1)-adenosine antagonist, In contrast, the infusion of N-6-cyclohexyladenosine (CHA), a selective A(2)-adenosine agonist, at 2 pmol/min significantly suppressed SWS before causing an increase in SWS, and a decrease in PS was also markedly visible, Essentially the same effects of CGS21680 and CHA were observed when these compounds were administered to the parenchymal region of the rostral basal forebrain through chronically implanted microdialysis probes, Thus, we clearly showed that stimulation of A(2a)-adenosine receptors in the rostral basal forebrain promotes SWS and PS, Furthermore, i.p. injections of KF17837 at 30 and 100 mg/kg of body weight dose-dependently attenuated the magnitude of the SWS increase produced by the infusion of PGD(2) into the subarachnoid space of the sleep-promoting zone, thus indicating that the A(2a)-adenosine receptors are crucial in the sleep-promoting process triggered by PGD(2).