EFFECT OF DIFFERENT XANTHINES AND PHOSPHODIESTERASE INHIBITORS ON C-FOS EXPRESSION IN RAT STRIATUM

It has previously been shown that caffeine, in a dose-dependent manner , increases the expression of the protooncogene c-fos in the rat brain , predominantly in the caudate-putamen and tuberculum olfactorium. In this study we examined the effect of related xanthines and of selectiv e phosphodiesterase inhibitors on c-fos expression. The effect of caff eine (75 mg kg(-1)) was mimicked by 3-isobutyl-1-methyl xanthine (IBMX ) (25 mg kg(-1)) and theophylline (100 mg kg(-1)) but not by 8-p-sulfo phenyltheophylline (10 mg kg(-1)), enprofylline, theobromine or paraxa nthine (each at 100 mg kg(-1)). Moreover, the cyclic AMP-selective pho sphodiesterase inhibitors rolipram (10 or 20 mg kg(-1)) and SQ 20006 ( 25 mg kg(-1)) and the cyclic GMP-selective phosphodiesterase inhibitor zaprinast (10 mg kg(-1)) failed to induce c-fos in striatum, but caus ed a clear-cut induction in the overlying cerebral cortex. Thus, c-fos is induced in rat striatum following adminstration of caffeine and ot her xanthines that (provided they enter the brain) block adenosine rec eptors, suggesting an involvement of central adenosine receptors. Inhi bition of cyclic nucleotide phosphodiesterase does not appear to play any important role in c-fos induction by the xanthines.