EFFECTS OF METHYLPHENIDATE ON REGIONAL BRAIN GLUCOSE-METABOLISM IN HUMANS - RELATIONSHIP TO DOPAMINE D-2 RECEPTORS

Objective: The authors' goals were to determine whether baseline dopam ine activity contributes to response to methylphenidate and to assess the pattern of metabolic responses associated with enhanced dopamine a ctivity. Method: They used positron emission tomography with 2-deoxy-2 [18F]fluoro-D-glucose to evaluate the effects of two sequential doses of methylphenidate on brain metabolism in 15 healthy subjects. Dopamin e D-2 receptor availability was measured with [11C]raclopride to evalu ate its relation to methylphenidate-induced metabolic changes. Results : Methylphenidate increased brain metabolism in six subjects, decrease d it in two, and did not change it in seven; however, it consistently increased cerebellar metabolism. Methylphenidate significantly increas ed ''relative'' (region relative to the whole brain) metabolism in the cerebellum and decreased it in the basal ganglia. Regional metabolic changes in the cerebellum and the frontal and temporal cortices were s ignificantly correlated with D-2 availability. Frontal and temporal me tabolism were increased in subjects with high D-2 receptors and decrea sed in subjects with low D-2 receptors. Conclusions: Methylphenidate i nduced variable changes in brain metabolism, but it consistently incre ased cerebellar metabolism. It also induced a significant reduction in relative metabolism in the basal ganglia. The significant association between metabolic changes in the frontal and temporal cortices and in the cerebellum and D-2 receptors suggests that methylphenidate's meta bolic effects in these brain regions are due in part to dopamine chang es and that differences in D-2 receptors may be one of the mechanisms accounting for the variability in response to methylphenidate.