Blockade of A1 receptors by caffeine induces c-fos, zif-268 and ARC expression in the striatum through different interactions with the dopamine system.

Abstract

Altogether, these results demonstrate that caffeine- and DPCPX-mediated IEG inductions involved different mechanisms in striatonigral and striatopallidal neurons through blockade of A1 receptors. IEG inductions result from a stimulation of dopamine release in striatonigral neurons and from activation of glutamate release and probably also acetylcholine release in striatopallidal neurons. Acute blockade of A1 receptors induces high striatal expression of transcription factors IEG from leucine zipper (c-fos) and zinc finger (zif-268) families and this expression could reflect the behavioral depression induced by high dose of caffeine. These transcription factors could also be involved in the plastic changes resulting from a chronic treatment with caffeine such as the variations in several receptors and G protein sububits16 which may be involved in the development of tolerance to caffeine. Moreover, A2A receptor-deficient mice showed unexpected alterations in striatal gene expression or motor behavior probably related to adaptative changes in which A1 receptors might be involved.17