Accumulation of alpha-synuclein is the pathological hallmark of several movement disorders including Parkinson’s disease (PD), dementia with Lewy bodies and multiple system atrophy. PD is characterized clinically by motor impairment (akinesia, bradykinesia, rigidity, postural instability) and pathologically by the widespread occurrence of alpha-synuclein positive inclusions (Lewy bodies) and neurodegeneration in selected brain regions including the substantia nigra (SN) and locus coeruleus (LC). Mice overexpressing human wild-type alpha-synuclein (Thy-1 promoter) display early and progressive sensorimotor impairments (Fleming et al., 2004) and deficits in olfaction and anxiety tests (Fleming et al. SFN abst. ’05). We have assessed the effects of alpha-synuclein overexpression (Rockenstein et al., 2002) on nigrostriatal function with radioligand binding for dopamine transporter (DAT: GBR-12395, 1, 2, 5, 10, 15, 20 nM) and vesicular monoamine transporter 2 (VMAT-2: dihydroterabenazine, 1, 2, 5, 10, 15, 20 nM...