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DARPP Chocolate: A Caffeinated Morsel of Striatal Signaling

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 A2A 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 A2A receptor blockade, but leave open the possibility that antagonism of presynaptic or postsynaptic A1 receptors also contributes to DARPP-32-dependent psychomotor stimulation by caffeine.

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Classifications


Resource Type: Diagram, Illustration, Journal article/Issue, Review
Audience Level: Undergraduate upper division 15-16, Graduate, Professional (degree program)

Author and Copyright


Authors and Editors: Elena Bastia of Center for Aging, Massachusetts General Hospital, Michael A. Schwarzschild of Genetics and Neurodegeneration, Massachusetts General Hospital
Publisher: American Association for the Advancement of Science
Format: application/pdf, image/gif, image/jpeg, text/html
Copyright and other restrictions: Yes
Cost: Yes

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