Parkinsonian patients report blunted subjective effects of methylphenidate

Mesolimbic-mesocortical dopamine brain circuits important for psychostimulant reward in animals are developed to greater extents in humans. Brains of patients with Parkinson's disease show depletion of ventral tegmental area mesolimbic-mesocortical neurons. The authors assessed psychostimulant responses in parkinsonian patients to test whether intact dopaminergic systems are required for subjective psychostimulant effects. Responses to placebo and 15, 20, 25, and 30 mg of methylphenidate were studied in 12 parkinsonian patients and 12 neurologically intact matched controls. Physiological and subjective mood responses were recorded using the Profile of Mood States, Addiction Research Center Inventory, and Visual Analog Scale. Drug-induced changes in "good" feelings and overall drug responses were attenuated in the parkinsonian patients. These results, in conjunction with animal data, provide support for dopamine hypotheses of psychostimulant reward in humans and suggest possible bases for some of the mood disturbances found in many parkinsonian patients.