title: An adenosine A receptor agonist induces sleep by increasing GABA release in the tuberomammillary nucleus to inhibit histaminergic systems in rats.
abstract: The adenosine A(2A) receptor (A(2A)R) has been demonstrated to play a crucial role in the regulation of the sleep process. However, the molecular mechanism of the A(2A)R-mediated sleep remains to be elucidated. Here we used electroencephalogram and electromyogram recordings coupled with in vivo microdialysis to investigate the effects of an A(2A)R agonist, CGS21680, on sleep and on the release of histamine and GABA in the brain. In freely moving rats, CGS21680 applied to the subarachnoid space underlying the rostral basal forebrain significantly promoted sleep and inhibited histamine release in the frontal cortex. The histamine release was negatively correlated with the amount of non-rapid eye movement sleep (r = - 0.652). In urethane-anesthetized rats, CGS21680 inhibited histamine release in both the frontal cortex and medial pre-optic area in a dose-dependent manner, and increased GABA release specifically in the histaminergic tuberomammillary nucleus but not in the frontal cortex. Moreover, the CGS21680-induced inhibition of histamine release was antagonized by perfusion of the tuberomammillary nucleus with a GABA(A) antagonist, picrotoxin. These results suggest that the A(2A)R agonist induced sleep by inhibiting the histaminergic system through increasing GABA release in the tuberomammillary nucleus.
authors.affiliation: School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Zong-Yuan
authors.initials: ZY
authors.lastname: Hong
authors.forename: Zhi-Li
authors.initials: ZL
authors.lastname: Huang
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Qu
authors.forename: Naomi
authors.initials: N
authors.lastname: Eguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Urade
authors.forename: Osamu
authors.initials: O
authors.lastname: Hayaishi
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058908:Adenosine A2 Receptor Agonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006632:Histamine / Q000378:metabolism*; D007026:Hypothalamic Area, Lateral / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects* / Q000378:metabolism; D010627:Phenethylamines / Q000494:pharmacology; D011301:Preoptic Area / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D058908:Adenosine A2 Receptor Agonists; D000959:Antihypertensive Agents; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; D011963:Receptors, GABA-A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D000241:Adenosine