Role of adenosine A 1 receptor in the perifornical–lateral hypothalamic area in sleep–wake regulation in rats

Abstract

The perifornical–lateral hypothalamic area (PF-LHA) has been implicated in the regulation of arousal. The PF-LHA contains wake-active neurons that are quiescent during non-REM sleep and in the case of neurons expressing the peptide hypocretin (HCRT), quiescent during both non-REM and REM sleep. Adenosine is an endogenous sleep factor and recent evidence suggests that adenosine via A 1 receptors may act on PF-LHA neurons to promote sleep. We examined the effects of bilateral activation as well as blockade of A 1 receptors in the PF-LHA on sleep–wakefulness in freely behaving rats. The sleep–wake profiles of male Wistar rats were recorded during reverse microdialysis perfusion of artificial cerebrospinal fluid (aCSF) and two doses of adenosine A 1 receptor antagonist, 1,3-dipropyl-8-phenylxanthine (CPDX; 5 μM and 50 μM) or A 1 receptor agonist, N 6-cyclopentyladenosine (CPA; 5 μM and 50 μM) into the PF-LHA for 2 h followed by 4 h of aCSF perfusion. CPDX perfused into the PF-LHA during lights-on phase produced arousal ( F = 7.035, p < 0.001) and concomitantly decreased both non-REM ( F = 7.295, p < 0.001) and REM sleep ( F = 3.456, p < 0.004). In contrast, CPA perfused into the PF-LHA during lights-off phase significantly suppressed arousal ( F = 7.891, p < 0.001) and increased non-REM ( F = 8.18, p <0.001) and REM sleep ( F = 30.036, p < 0.001). These results suggest that PF-LHA is one of the sites where adenosine, acting via A 1 receptors, inhibits PF-LHA neurons to promote sleep.