CAFFEINE REGULATES NEUROTENSIN AND CHOLECYSTOKININ MESSENGER-RNA EXPRESSION IN THE RAT STRIATUM

Interactions between dopamine and neurotensin or dopamine and cholecys tokinin have been demonstrated in the basal ganglia. Disruption of nig rostriatal dopaminergic transmission results in a dramatic increase in neurotensin messenger RNA and in an induction of cholecystokinin mess enger RNA in the striatum. Interaction between striatal dopaminergic a nd adenosinergic systems have also been reported. Adenosine and the ad enosine receptor antagonist, caffeine, regulate gene expression in the striatum. In the present study, in situ hybridization histochemistry was used to investigate the putative regulation of neurotensin and cho lecystokinin messenger RNA expression by caffeine in the rat striatum. Using this method, cholecystokinin messenger RNA was undetectable and neurotensin messenger RNA very sparse in the normal striatum. Chronic caffeine administration induced a dramatic increase in neurotensin me ssenger RNA in the subcallosal region of the caudate-putamen and a mod erate increase in the shell sector of the accumbens nucleus. Similarly , caffeine induced a significant striatal expression of cholecystokini n messenger RNA in the dorsolateral and ventrolateral quadrants but wa s not restricted to the subcallosal area. At the cellular level, this coresponded to a significant labeling of a moderate to high density of medium-sized striatal neurons. These distributions were identical to those of neurotensin and cholecystokinin messenger RNAs observed in th e case of disruption of dopaminergic transmission. We therefore conclu ded that in the intact striatum normally innervated by dopaminergic fi bers, caffeine, probably acting through a presynaptic A2 receptor, ind uced a relative dopamine depletion which in turn led to the induction of neurotensin and cholecystokinin expression in subsets of striatal n eurons.