Citation

Lazarus M, Shen HY, Cherasse Y, Qu WM, Huang ZL, Bass CE, Winsky-Sommerer R, Semba K, Fredholm BB, Boison D, Hayaishi O, Urade Y, Chen JF. J. Neurosci. 2011; 31(27): 10067-10075.

Affiliation

Department of Molecular Behavioral Biology, Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan, Department of Neurology, Boston University School of Medicine, Boston, Massachusetts 02118, R. S. Dow Neurobiology Laboratories, Legacy Research Institute, Portland, Oregon 97232, Department of Pharmacology, Fudan University Shanghai Medical College, Shanghai 200032, China, Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, United Kingdom, Department of Anatomy and Neurobiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia B3H 1X5, Canada, and Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm SE-171 77, Sweden.

Copyright

(Copyright © 2011, Society for Neuroscience)

DOI

10.1523/JNEUROSCI.6730-10.2011

PMID

21734299

PMCID

PMC3153505

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.

Language: en