Caffeine as a psychomotor stimulant: mechanism of action

Cell Mol Life Sci. 2004 Apr;61(7-8):857-72. doi: 10.1007/s00018-003-3269-3.


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 A(1) and A(2A) 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 A(2A) 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine A1 Receptor Antagonists*
  • Adenosine A2 Receptor Antagonists*
  • Animals
  • Basal Ganglia / cytology
  • Basal Ganglia / metabolism
  • Caffeine / metabolism*
  • Caffeine / pharmacology*
  • Central Nervous System Stimulants / metabolism*
  • Dopamine / metabolism
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Enzyme Inhibitors / metabolism
  • Humans
  • Motor Activity / drug effects*
  • Nerve Tissue Proteins*
  • Neurons / metabolism
  • Neuroprotective Agents / metabolism
  • Parkinson Disease / metabolism
  • Phosphoproteins / metabolism
  • Receptor, Adenosine A1 / metabolism
  • Receptor, Adenosine A2A / metabolism
  • Receptors, Dopamine D2 / metabolism
  • Signal Transduction
  • Synaptic Transmission / physiology


  • Adenosine A1 Receptor Antagonists
  • Adenosine A2 Receptor Antagonists
  • Central Nervous System Stimulants
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Enzyme Inhibitors
  • Nerve Tissue Proteins
  • Neuroprotective Agents
  • Phosphoproteins
  • Receptor, Adenosine A1
  • Receptor, Adenosine A2A
  • Receptors, Dopamine D2
  • Caffeine
  • Dopamine