A1 receptor mediated adenosinergic regulation of perifornical–lateral hypothalamic area neurons in freely behaving rats

Abstract The perifornical–lateral hypothalamic area (PF-LHA) plays a central role in the regulation of behavioral arousal. The PF-LHA contains several neuronal types including wake-active hypocretin (HCRT) neurons that have been implicated in the promotion and/or maintenance of behavioral arousal. A...

Full description

Saved in:
Bibliographic Details
Published in:Neuroscience 2010-04, Vol.167 (1), p.40-48
Main Authors: Rai, S, Kumar, S, Alam, M.A, Szymusiak, R, McGinty, D, Alam, M.N
Format: Article
Language:English
Subjects:
Adenosine - analogs & derivatives
Adenosine - pharmacology
Adenosine A1 Receptor Agonists
Adenosine A1 Receptor Antagonists
Animals
Biological and medical sciences
Catheterization
Central Nervous System Agents - pharmacology
Electrodes, Implanted
Fundamental and applied biological sciences. Psychology
Hypothalamus - drug effects
Hypothalamus - physiology
Intracellular Signaling Peptides and Proteins - metabolism
Light
Male
Microdialysis
Microelectrodes
Neurology
Neurons - drug effects
Neurons - physiology
Neuropeptides - metabolism
Orexins
Photoperiod
Proto-Oncogene Proteins c-fos - metabolism
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A1 - metabolism
Sleep - drug effects
Sleep - physiology
Sleep. Vigilance
Vertebrates: nervous system and sense organs
Wakefulness - drug effects
Wakefulness - physiology
Xanthines - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Abstract The perifornical–lateral hypothalamic area (PF-LHA) plays a central role in the regulation of behavioral arousal. The PF-LHA contains several neuronal types including wake-active hypocretin (HCRT) neurons that have been implicated in the promotion and/or maintenance of behavioral arousal. Adenosine is an endogenous sleep factor and recent evidence suggests that activation and blockade of adenosine A1 receptors within the PF-LHA promote and suppress sleep, respectively. Although, an in vitro study indicates that adenosine inhibits HCRT neurons via A1 receptor, the in vivo effects of A1 receptor mediated adenosinergic transmission on PF-LHA neurons including HCRT neurons are not known. First, we determined the effects of N6 -cyclopentyladenosine (CPA), an adenosine A1 receptor agonist, on the sleep–wake discharge activity of the PF-LHA neurons recorded via microwires placed adjacent to the microdialysis probe used for its delivery. Second, we determined the effects of CPA and that of an A1 receptor antagonist, 1,3-dipropyl-8-phenylxanthine (CPDX) into the PF-LHA on cFos-protein immunoreactivity (Fos-IR) in HCRT and non-HCRT neurons around the microdialysis probe used for their delivery. The effect of CPA on Fos-IR was studied in rats that were kept awake during lights-off phase, whereas the effect of CPDX was examined in undisturbed rats during lights-on phase. CPA significantly suppressed the sleep–wake discharge activity of PF-LHA neurons. Doses of CPA (50 μM) and CPDX (50 μM) that suppressed and induced arousal, respectively, in our earlier study [Alam MN, Kumar S, Rai S, Methippara M, Szymusiak R, McGinty D (2009) Brain Res 1304:96–104], significantly suppressed and increased Fos-IR in HCRT and non-HCRT neurons. These findings suggest that wake-promoting PF-LHA system is subject to increased endogenous adenosinergic inhibition and that adenosine acting via A1 receptors, in part, inhibits HCRT neurons to promote sleep.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2010.01.044