Assessment of methylphenidate-induced changes in binding of continuously infused [C-11]-raclopride in healthy human subjects: correlation with subjective effects

Rationale: The dopaminergic system has been implicated in the pathogenesis and treatment of a variety of neuropsychiatric disorders. It has been shown that information on endogenous dopamine (DA) release can be obtained noninvasively by combining positron emission tomography with a dopaminergic challenge. This approach is based on the assumption that an injected radiolabeled ligand competes with the neurotransmitter for the same receptor. Increases in DA release will therefore result in a decreased binding of the radioligand.Objectives: We investigated the effect of the DA reuptake blocker methylphenidate (MP) on the binding of the D-2 receptor ligand [C-11]-raclopride (RAC). Methods: The effect of a 0.25 mg/kg intravenous dose of MP was studied in six healthy volunteers. RAC was administered as a bolus followed by constant infusion, and subjective effects were assessed using verbal rating scales. Results: Control scans without MP administration showed that the mean RAC binding reached stable values approximately 30 min after start of the infusion. MP administration induced a 24% decrease in RAC binding in the total striatum. Correlations were found between the MP-induced change in euphoria and the percent change in binding potential (Delta BP) in the dorsal striatum and between baseline anxiety and Delta BP in the dorsal and middle striatum. We also found a negative correlation between baseline BP in the dorsal striatum and change in euphoria. Conclusions: Our results comply with previous findings, indicating the feasibility of the bolus infusion design combined with a relatively low MP dose to study dopaminergic (dys)function.