AP-2beta modulation of Dopamine Turnover and the response to Methylphenidate: An [18F]FDOPA-PET study

301 Objectives AP-2β is a transcription factor, which is involved in the transcribing proteins amongst others from the catecholaminergic system. Earlier studies showed that AP-2β correlates with MAO activity and dopamine (DA) metabolites (DOPAC+HVA). Stimulation of the DA System with Methylphenidate (MPH) in PET studies, indicate increased striatal DA and a decreased DA turnover under MPH. Until now, the genetic poymorphism AP-2β and the DA system are not investigated in-vivo with [18F]FDOPA-PET. Methods 30 healthy women underwent 2 [18F]FDOPA-PET scans (124 min; slow bolus-injection; art. blood sampling; metabolite det.) in randomized order (no-drug/oral MPH 0.5mg/kg). Genetic analyses for AP-2β, MAO-A and COMT were previously done. After preprocessing (movement correction, co-registration, spatial normalization) time activity curves (TAC) were obtained for ventral putamen and caudate. These TACs were analyzed according to the reversible ‘inlet/outlet-model9 to obtain regional net-uptake of [18F]FDOPA (K), Vd and kloss. Also voxel based morphometry (VBM) analysis was conducted. Results Results show a decrease in kloss under MPH in PU and CN (~15%). Analyses of the AP-2β revealed at baseline a sign. difference in kloss between homozygous groups (p=.024; short allele carrier (SAC): higher kloss) and Vt (p=.013; SAC: lower Vd). Additionally there is a trend in ΔK (p=.052), which gets more pronounced, if only the ‘normal order of treatment’ group (BL/MPH) is analyzed (p=.039). Conclusions The results show:AP-2s is affecting the DA turnover and supporting earlier findings. SAC have a higher kloss and are associated with higher MAO activity and better cognitive performance. Long allele carrier show lower kloss. From earlier studies we know that they are associated with binge eating disorder. Those patients show lower DA metabolites and HVA in CFS. Supporting the hypotheis that AP2β is an important gene for the DA system. Research Support DFG, VE 466/2-1& IRTG 1328 & IZKF, RWTH Aachen University