Microinjection of Adenosine into the Hypothalamic Ventrolateral Preoptic Area Enhances Wakefulness via the A 1 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.