Alpha-synuclein (ASYN) is a presynaptic neuronal protein related genetically and neuropathologically to Parkinson's disease (PD). However, the role of ASYN in the selective degeneration of specific neuronal populations such as the loss of dopamine (DA) neurons in the substantia nigra pars compacta (SNc) remains elusive. Since previous strategies for viral overexpression of ASYN in animals are not cell-type specific, we generated novel adeno-associated viral vectors (AAV) to Cre-dependently express human wild-type ASYN (ASYN-WT) or ASYN with pathogenic A53T or A30P mutations. This strategy allowed us to restrict ASYN expression to cells expressing Cre recombinase only and hence to investigate the cell-autonomous effects of elevated ASYN levels in genetically-defined cell populations. To test the specificity of our vectors, we restricted ASYN overexpression to various cell types in defined anatomical regions by stereotaxic intracranial infusion of AAVs in different Cre driver lines. Here, we characterized in more detail ASYN-WT overexpression in DA neurons of the SNc. In DATCre mice, overexpression of ASYN-WT led to increased levels of ASYN phosphorylated at serine 129 and elevated locomotor activity in the open-field 30 and 90 days after viral infusion. Neurochemical analysis of DA tissue levels indicated significantly increased striatal DA after overexpression of ASYN-WT suggesting elevated vesicular DA stores. Histopathological investigations indicated no major alterations in DA neuron numbers in the SNc 90 days post infusion. We conclude that overexpression of ASYN in DA neurons is associated with hyperdopaminergia and does not suffice to cause major degeneration up to 90 days after virus infusion.