Adenosine sleep theory: how I postulated it

Abstract

for EEG and EMG recordings. We selected two types of adenosine agonists: adenosine A1 receptor stimulants, L-phenylisopropyl adenosine (L-PIA) and N 6 cyclohexyladenosine (CHA), and adenosine A1 and A2 receptor stimulant 5’-N-ethylcarboxamidoadenosine (NECA). The results showed that all three agents increased deep slow wave sleep (SWS) and reduced rapid eye movement (REM) sleep 10 . Although the agents decreased REM sleep, which occupies 15% of the total sleep in rats, the finding was of interest because the total amount of sleep was significantly increased. In order to test the role of endogenous adenosine in sleep, we administered to rats implanted for polygraphic recordings, deoxycoformycin, a potent inhibitor of adenosine deaminase, which would be expected to increase the levels of adenosine in the central nervous system (CNS). We administered two doses (0.5 or 2.0 mg/kg) of the drug i.p. and polygraphically recorded animals for 6 hours. The smaller dose of deoxycoformycin increased only REM sleep, whereas the higher dose increased SWS 11 . Those results were consistent with our previous experiments with adenosine analogs and indicated a sleep-inducing role for endogenous adenosine.