Acute and sustained effects of methylphenidate on cognition and presynaptic dopamine metabolism: an [18F]FDOPA PET study.
Methylphenidate (MPH) inhibits the reuptake of dopamine and noradrenaline. PET studies with MPH challenge show increased competition at postsynaptic D2/3-receptors, thus indirectly revealing presynaptic dopamine release. We used [ 18F]fluorodopamine ([ 18F]FDOPA)-PET in conjunction with the inlet– outlet model (IOM) of Kumakura et al. (2007) to investigate acute and long-term changes in dopamine synthesis capacity and turnover in nigrostriatal fibers of healthy subjects with MPH challenge. Twenty healthy human females underwent two dynamic [ 18F]FDOPA PET scans (124 min; slow bolus-injection; arterial blood sampling), with one scan in untreated baseline condition and the other after MPH administration (0.5 mg/kg, p.o.), in randomized order. Subjects underwent cognitive testing at each PET session. Time activity curves were obtained for ventral putamen and caudate and were analyzed according tothe IOMto obtainthe regional net-uptake of [ 18F]FDOPA (K;dopamine synthesis capacity) aswell asthe [ 18F]fluorodopaminewashout rate (kloss, index of dopamine turnover). MPH substantially decreased kloss in putamen (22%; p 0.003). In the reversed treatment order group (MPH/no drug), K was increased by 18% at no drug follow-up. The magnitude of K at the no drug baseline correlated with cognitive parameters. Furthermore, individual klosschanges correlated with altered cognitive performance under MPH. [ 18F]FDOPA PET in combination with the IOM detects an MPH-evoked decrease in striatal dopamine turnover, in accordance with the known acute pharmacodynamics of MPH. Furthermore, the scan-ordering effect on K suggested that a single MPH challenge persistently increased striatal dopamine synthesis capacity. Attenuation of dopamine turnover by MPH is linked to enhanced cognitive performance in healthy females.
|Keywords||[18F]FDOPA PET, cognition, dopamine turnover, long-term effects, methylphenidate, stimulants|
|Journal||The Journal of Neuroscience|
Schabram, I., Henkel, K., Mohammadkhani Shali, S., Dietrich, C, Schmaljohann, J., Winz, O., … Vernaleken, I. (2014). Acute and sustained effects of methylphenidate on cognition and presynaptic dopamine metabolism: an [18F]FDOPA PET study. The Journal of Neuroscience. Retrieved from http://hdl.handle.net/1765/125231