Arousal Effect of Caffeine Depends on Adenosine A2A Receptors in the Shell of the Nucleus Accumbens
Copyright policy )Arousal Effect of Caffeine Depends on Adenosine A2A Receptors in the Shell of the Nucleus Accumbens
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.
- Boston College United States
- Boston University United States
- Wake Forest University United States
- Shanghai Medical College of Fudan University China (People's Republic of)
- Fudan University China (People's Republic of)
Mice, Knockout, Analysis of Variance, Dose-Response Relationship, Drug, Electromyography, Green Fluorescent Proteins, Electroencephalography, Mice, Transgenic, Basal Ganglia, Choline O-Acetyltransferase, Mice, Inbred C57BL, Mice, Mutagenesis, Caffeine, Mutation, Animals, Humans, Central Nervous System Stimulants, Arousal, Locomotion, Cell Line, Transformed
Mice, Knockout, Analysis of Variance, Dose-Response Relationship, Drug, Electromyography, Green Fluorescent Proteins, Electroencephalography, Mice, Transgenic, Basal Ganglia, Choline O-Acetyltransferase, Mice, Inbred C57BL, Mice, Mutagenesis, Caffeine, Mutation, Animals, Humans, Central Nervous System Stimulants, Arousal, Locomotion, Cell Line, Transformed
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