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Caffeine as a psychomotor stimulant: mechanism of action


The popularity of caffeine as a psychoactive drug is due to its stimulant properties, which depend on its ability to reduce adenosine transmission in the brain. Adenosine A1 and A2A receptors are expressed in the basal ganglia, a group of structures involved in various aspects of motor control. Caffeine acts as an antagonist to both types of receptors. Increasing evidence indicates that the psychomotor stimulant effect of caffeine is generated by affecting a particular group of projection neurons located in the striatum, the main receiving area of the basal ganglia. These cells express high levels of adenosine A2A receptors, which are involved in various intracellular processes, including the expression of immediate early genes and regulation of the dopamine- and cyclic AMP-regulated 32-kDa phosphoprotein DARPP-32. The present review focuses on the effects of caffeine on striatal signal transduction and on their involvement in caffeine-mediated motor stimulation.

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Correspondence to G. Fisone.

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Received 8 July 2003; received after revision 7 September 2003; accepted 6 October 2003

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Fisone, G., Borgkvist, A. & Usiello, A. Caffeine as a psychomotor stimulant: mechanism of action. CMLS, Cell. Mol. Life Sci. 61, 857–872 (2004).

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  • Basal ganglia
  • adenosine
  • adenosine A2A receptors
  • immediate early gene
  • dopamine
  • dopamine- and cAMP-regulated phosphoprotein of 32 kDa
  • motor activity
  • Parkinson’s disease