Role of adenosine A(1) receptor in the perifornical-lateral hypothalamic area in sleep-wake regulation in rats.
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 microM and 50 microM) or A(1) receptor agonist, N(6)-cyclopentyladenosine (CPA; 5 microM and 50 microM) 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.
Research Service (151A3), Veterans Affairs Greater Los Angeles Healthcare System, 16111 Plummer Street, Sepulveda, CA 91343, USA. noor@ucla.edu
Md Noor
MN
Alam
Sunil
S
Kumar
Seema
S
Rai
Melvi
M
Methippara
Ronald
R
Szymusiak
Dennis
D
McGinty
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D002404:Catheterization; D002491:Central Nervous System Agents / Q000494:pharmacology; D007026:Hypothalamic Area, Lateral / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010775:Photic Stimulation; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*; D014970:Xanthines / Q000494:pharmacology
D058907:Adenosine A1 Receptor Agonists; D058916:Adenosine A1 Receptor Antagonists; D002491:Central Nervous System Agents; D043682:Receptor, Adenosine A1; D014970:Xanthines; C048599:N(6)-cyclopentyladenosine; C049140:1,3-dipropyl-8-phenylxanthine; D000241:Adenosine