Caffeine-mediated induction of c-fos, zif-268 and arc expression through A(1) receptors in the striatum: different interactions with the dopaminergicsystem

Adenosine and the adenosine receptor antagonist, caffeine, modulate locomot or activity and striatal neuropeptide expression through interactions with the dopaminergic system by mechanisms which remain partially undetermined. We adressed this question by using quantitative immunocytochemistry and in situ hybridization, combined with retrograde tracing of striatal neurons, t o characterize the mechanism(s) leading to the striatal increase in the imm ediate early genes (IEG), c-fos, zif-268 and arc, following a single inject ion of caffeine or the A(1) antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). Caffeine and DPCPX induced c-fos, zif-268 and arc expression, both at mRNA and protein levels, in large proportions of striatonigral and stri atopallidal neurons. The involvement of dopamine systems was evaluated by m anipulations of the dopaminergic transmission. Quinpirole, a D-2 agonist, a lmost completely blocked the caffeine-induced IEG increase in both striatop allidal and striatonigral neurons. Conversely, the lesion of the nigrostria tal pathway and the D-1 antagonist SCH23390 abolished the caffeine effects in striatonigral neurons but had no or slight effect, respectively, on its action in striatopallidal neurons. These observations demonstrate that caff eine- and DPCPX-mediated IEG inductions involved different mechanisms in st riatonigral and striatopallidal neurons through blockade of A(1) receptors. Immediate early gene inductions result from a stimulation of dopamine rele ase in striatonigral neurons and from activation of glutamate release and p robably also acetylcholine release in striatopallidal neurons. These result s also support the idea that, besides A(2A) receptors, adenosine acting at the A(1) receptor plays pivotal functions in the basal ganglia physiology a nd that blockade of these receptors by specific or nonspecific antagonists, DPCPX and caffeine, may influence a broad range of neuronal functions in t he striatum.