Changes in psychomotor effects of L-dopa and methylphenidate after sustained dopaminergic therapy in Parkinson's disease

Background: Sustained drug therapy in Parkinson’s disease may alter the psychomotor responses to acute challenges with dopaminergic drugs, L-dopa and methylphenidate, and cause cross sensitisation. Methods: The mood, psychomotor and reward potentiating effects of an acute challenge with L-dopa and methylphenidate on separate occasions were assessed under double blind (medication naïve) conditions after a placebo and then the testing sessions were repeated in the same (medication experienced) patients following a median period of 16.7 months of continuous dopaminergic drug therapy. Results: In the medication naïve condition, affect was not changed by L-dopa or methylphenidate and only L-dopa improved motor function. In the medication experienced condition, active drugs improved positive affect compared with the medication naïve condition and there was an enhanced effect of L-dopa on motor function. Reward responsivity was enhanced by both L-dopa and methylphenidate in medication naïve and experienced conditions. Conclusion: Sustained dopaminergic drug therapy augments the motor effects of an acute challenge with L-dopa and induces euphoriant effects to L-dopa and methylphenidate challenges