Influence of repeated exposure to caffeine on dopamine transmission: preclinical evidence and potential consequences of caffeine consumption

Caffeine is a most popular psychostimulant and is consumed worldwide. A large body of evidence demonstrates the existence of striking differences between the effects of caffeine and those of psychostimulants bearing abuse potential, like amphetamines and cocaine, a major one being that the reinforcing properties of caffeine are generally modest. Nevertheless, preclinical research has suggested that caffeine, similar to addictive psychostimulants, is capable of interacting with dopaminergic circuits in the brain and, accordingly, of influencing dopamine-mediated neurobehavioural functions. Here evidence is reported from an experimental model of long-term caffeine administration in the rat which demonstrates that caffeine can exert an enduring facilitatory influence on dopamine transmission in the corpus striatum. Such an effect was found to be manifested as the development of sensitization to caffeine-induced motor stimulant effects, and as the onset of modifications involving receptors and immediate early gene expression in the striatum. Moreover, an increased responsiveness to the motor stimulation and striatal immediate early gene expression elicited by D-amphetamine was observed in rats pre-exposed to caffeine, further supporting the ability of caffeine to induce a hyperfunctionality of dopamine transmission. Taken together, these results lend support to the hypothesis that caffeine consumption might represent a factor capable of amplifying certain behaviour