Arousal effect of caffeine depends on adenosine A2A receptors in the shell of the nucleus accumbens

Michael Lazarus, Hai Ying Shen, Yoan Cherasse, Wei Min Qu, Zhi Li Huang, Caroline E. Bass, Raphaelle Winsky-Sommerer, Kazue Semba, Bertil B. Fredholm, Detlev Boison, Osamu Hayaishi, Yoshihiro Urade, Jiang Fan Chen

Research output: Contribution to journalArticlepeer-review

188 Scopus citations


Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosineA2A receptors (A2ARs) 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 A2ARs in rats by local infection with adeno-associated virus carrying short-hairpin RNA, we report that theA2ARs 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 A2ARs were focally removed from the NAc core or other A2AR-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.

Original languageEnglish (US)
Pages (from-to)10067-10075
Number of pages9
JournalJournal of Neuroscience
Issue number27
StatePublished - Jul 6 2011
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)


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