Microinjection of Adenosine into the Hypothalamic Ventrolateral Preoptic Area Enhances Wakefulness via the A1 Receptor in Rats

Adenosine (AD) is a nucleic acid component that is critical for energy metabolism in the body. AD modulates numerous neural functions in the central nervous system, including the sleep-wake cycle. Previous studies have indicated that the A(1) receptor (A(1)R) or A(2A) receptor (A(2A)R) may mediate the effects of AD on the sleep-wake cycle. The hypothalamic ventrolateral preoptic area (VLPO) initiates and maintains normal sleep. Histological studies have shown A(1)R are widely expressed in brain tissue, whereas A(2A)R expression is limited in the brain and undetectable in the VLPO. We hypothesize therefore, that AD modulates the sleep-wake cycle through A(1)R in the VLPO. In the present study, bilateral microinjection of AD or an AD transporter inhibitor (s-(4-nitrobenzyl)-6-thioinosine) into the VLPO of rats decreased non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. An A(1)R agonist (N-6-cyclohexyladenosine) produced similar effects in the VLPO. Microinjection of an A(1)R antagonist (8-cyclopentyl-1,3-dimethylxanthine) into the VLPO enhanced NREM sleep and diminished AD-induced wakefulness. These data indicate that AD enhances wakefulness in the VLPO via A(1)R in rats.