Caffeine and the Regulation of Locomotor Activity / Summary

In addition to modulating dopaminergic processes, caffeine shows neuroprotective efficacy in animal models of PD. In mice with neurotoxin-induced damage, caffeine acts in a dose-dependent manner to reduce the loss of endogenous dopamine and the dopamine transporter in mouse striatum. Striatal A_2AAR has been proposed to promote glutamate release and glia-mediated inflammation, which contribute to the pathogenesis of PD. Studies showing a significant reduction in risk of PD in populations with regular caffeine intake support a neuroprotective effect of caffeine against the development or exacerbation of PD. In an animal model, the neuroprotective effects of caffeine were mimicked by A_2AAR but not A₁AR antagonists, suggesting that A_2AAR blockade predominates in the antiPD effect of caffeine.

In summary, adenosine and dopamine receptors in the striatum actively participate in modulation of behavioral activation. Striatal regulation of behavioral activation and locomotion is a complex process that involves multiple neurotransmitter systems. Complete understanding of caffeine's effects on these systems at a molecular level requires further study. 
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However, current information clearly demonstrates that caffeine exerts a strong and complex modulatory influence on striatal neurotransmission under both physiologic and pathologic conditions.