DARPP Chocolate: A Caffeinated Morsel of Striatal Signaling

Abstract

The psychomotor stimulant effects of caffeine, the most widely consumed psychoactive substance, are mediated through its antagonism of extracellular adenosine receptors in the basal ganglia. In the absence of caffeine, adenosine stimulates inhibitory striatopallidal neurons that suppress motor activity by binding to A 2A receptors, thereby activating a cyclic adenosine 3′,5′-monophosphate (cAMP) and protein kinase A signaling pathway. Bastia and Schwarzschild discuss recent research implicating DARRP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kilodaltons) as an attractive mediator of the sustained psychomotor stimulant effect seen with low doses of caffeine. They highlight the role of postsynaptic A 2A receptor blockade, but leave open the possibility that antagonism of presynaptic or postsynaptic A 1 receptors also contributes to DARPP-32-dependent psychomotor stimulation by caffeine.