title: Adenosine A(2A) receptors regulate the activity of sleep regulatory GABAergic neurons in the preoptic hypothalamus.
abstract: The median preoptic nucleus (MnPN) and the ventrolateral preoptic area (VLPO) are two hypothalamic regions that have been implicated in sleep regulation, and both nuclei contain sleep-active GABAergic neurons. Adenosine is an endogenous sleep regulatory substance, which promotes sleep via A1 and A2A receptors (A2AR). Infusion of A2AR agonist into the lateral ventricle or into the subarachnoid space underlying the rostral basal forebrain (SS-rBF), has been previously shown to increase sleep. We examined the effects of an A2AR agonist, CGS-21680, administered into the lateral ventricle and the SS-rBF on sleep and c-Fos protein immunoreactivity (Fos-IR) in GABAergic neurons in the MnPN and VLPO. Intracerebroventricular administration of CGS-21680 during the second half of lights-on phase increased sleep and increased the number of MnPN and VLPO GABAergic neurons expressing Fos-IR. Similar effects were found with CGS-21680 microinjection into the SS-rBF. The induction of Fos-IR in preoptic GABAergic neurons was not secondary to drug-induced sleep, since CGS-21680 delivered to the SS-rBF significantly increased Fos-IR in MnPN and VLPO neurons in animals that were not permitted to sleep. Intracerebroventricular infusion of ZM-241385, an A2AR antagonist, during the last 2 h of a 3-h period of sleep deprivation caused suppression of subsequent recovery sleep and reduced Fos-IR in MnPN and VLPO GABAergic neurons. Our findings support a hypothesis that A2AR-mediated activation of MnPN and VLPO GABAergic neurons contributes to adenosinergic regulation of sleep.
authors: Research Service, Veteran Affairs Greater Los Angeles Healthcare System, Sepulveda, CA, USA.
authors: Sunil
authors: S
authors: Kumar
authors: Seema
authors: S
authors: Rai
authors: Kung-Chiao
authors: KC
authors: Hsieh
authors: Dennis
authors: D
authors: McGinty
authors: Md Noor
authors: MN
authors: Alam
authors: Ronald
authors: R
authors: Szymusiak
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D007031:Hypothalamus / Q000502:physiology*; D057967:Infusions, Intraventricular; D008297:Male; D008845:Microinjections; D023421:Models, Animal; D010627:Phenethylamines / Q000008:administration & dosage / Q000494:pharmacology; D011301:Preoptic Area / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000187:drug effects / Q000502:physiology*; D012890:Sleep / Q000187:drug effects / Q000502:physiology*; D014227:Triazines / Q000008:administration & dosage / Q000494:pharmacology; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D010627:Phenethylamines; D016760:Proto-Oncogene Proteins c-fos; D043705:Receptor, Adenosine A2A; D014227:Triazines; D014230:Triazoles; C097270:ZM 241385; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine
keywords: GABAergic neurons; c-Fos immunoreactivity; median preoptic nucleus; subarachnoid space; ventrolateral preoptic area
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