title: Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens.
abstract: Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the expression of A(2A)Rs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that the A(2A)Rs in the shell region of the nucleus accumbens (NAc) are responsible for the effect of caffeine on wakefulness. Caffeine-induced arousal was not affected in rats when A(2A)Rs were focally removed from the NAc core or other A(2A)R-positive areas of the basal ganglia. Our observations suggest that caffeine promotes arousal by activating pathways that traditionally have been associated with motivational and motor responses in the brain.
authors: Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
authors: Michael
authors: M
authors: Lazarus
authors: Hai-Ying
authors: HY
authors: Shen
authors: Yoan
authors: Y
authors: Cherasse
authors: Wei-Min
authors: WM
authors: Qu
authors: Zhi-Li
authors: ZL
authors: Huang
authors: Caroline E
authors: CE
authors: Bass
authors: Raphaelle
authors: R
authors: Winsky-Sommerer
authors: Kazue
authors: K
authors: Semba
authors: Bertil B
authors: BB
authors: Fredholm
authors: Detlev
authors: D
authors: Boison
authors: Osamu
authors: O
authors: Hayaishi
authors: Yoshihiro
authors: Y
authors: Urade
authors: Jiang-Fan
authors: JF
authors: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001143:Arousal / Q000187:drug effects*; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology*; D002461:Cell Line, Transformed; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016296:Mutagenesis; D009154:Mutation / Q000235:genetics; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D000697:Central Nervous System Stimulants; D034741:RNA, Small Interfering; D043705:Receptor, Adenosine A2A; D017448:Receptors, Dopamine D2; D049452:Green Fluorescent Proteins; D002110:Caffeine; D002795:Choline O-Acetyltransferase; D010751:Phosphopyruvate Hydratase