Adenosine A Receptor Deficiency Attenuates the Somnogenic Effect of Prostaglandin D in Mice

Prostaglandin D (PGD) is one of the most potent endogenous sleep promoting substances. PGD activates the PGD receptor (DPR) and increases the extracellular level of adenosine in wild-type (WT) mice but not DPR knockout (KO) mice, suggesting that PGD-induced sleep is DPR-dependent, and adenosine may be the signaling molecule that mediates the somnogenic effect of PGD. The aim of this study was to determine the involvement of the adenosine A receptor (AR) in PGD-induced sleep. We infused PGD into the lateral ventricle of WT and AR KO mice between 20:00 and 2:00 for 6 h, and electroencephalograms and electromyograms were simultaneously recorded. In WT mice, PGD infusion dose-dependently increased non-rapid eye movement (non-REM, NREM) sleep, which was 139.1%, 145.0% and 202.7% as large as that of vehicle-treated mice at doses of 10, 20 and 50 pmol/min, respectively. PGD infusion at doses of 20 and 50 pmol/min also increased REM sleep during the 6-h PGD infusion and 4-h post-dosing periods in WT mice to 148.9% and 166.7%, respectively. In AR KO mice, however, PGD infusion at 10 pmol/min did not change the sleep profile, whereas higher doses at 20 and 50 pmol/min increased the NREM sleep during the 6-h PGD infusion to 117.5% and 155.6%, respectively, but did not change the sleep in the post-dosing period. Moreover, PGD infusion at 50 pmol/min significantly increased the episode number in both genotypes but only enhanced the episode duration in WT mice. The results demonstrate that PGD-induced sleep in mice is mediated by both adenosine AR-dependent and -independent systems.