PT  - JOURNAL ARTICLE
AU  - Michael Lazarus
AU  - Hai-Ying Shen
AU  - Yoan Cherasse
AU  - Wei-Min Qu
AU  - Zhi-Li Huang
AU  - Caroline E. Bass
AU  - Raphaelle Winsky-Sommerer
AU  - Kazue Semba
AU  - Bertil B. Fredholm
AU  - Detlev Boison
AU  - Osamu Hayaishi
AU  - Yoshihiro Urade
AU  - Jiang-Fan Chen
TI  - Arousal Effect of Caffeine Depends on Adenosine A<sub>2A</sub> Receptors in the Shell of the Nucleus Accumbens
AID  - 10.1523/JNEUROSCI.6730-10.2011
DP  - 2011 Jul 06
TA  - The Journal of Neuroscience
PG  - 10067--10075
VI  - 31
IP  - 27
4099  - http://www.jneurosci.org/content/31/27/10067.short
4100  - http://www.jneurosci.org/content/31/27/10067.full
SO  - J. Neurosci.2011 Jul 06; 31
AB  - Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A2A 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 the A2ARs 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.