Caffeine mimics dopamine receptor agonists without stimulation of dopamine receptors.

The purpose of this study was to examine whether caffeine stimulates dopamine (DA) receptors. The effects of caffeine on the binding of [3H]spiperone to membranes from the striatum, accumulation of L-DOPA in the striatum in mice receiving gamma-butyrolactone, and regional levels of 3,4-dihydroxyphenylacetic acid in the brain of the rat were investigated and compared with those elicited by DA receptor agonists. Caffeine did not inhibit the binding of [3H]spiperone to membranes or the accumulation of L-DOPA in the striatum, produced by gamma-butyrolactone. Caffeine decreased the levels of 3,4-dihydroxyphenylacetic acid significantly in the striatum, olfactory tubercle and nucleus accumbens and slightly in the frontal cortex of rats, whereas it delayed utilization of DA in all those regions except the frontal cortex. Taken together these results suggest that caffeine fails to stimulate pre- or postsynaptic DA receptors. The possible mechanism by which caffeine mimics DA receptor in DA metabolism and behavior are discussed.