Alpha-synuclein is implicated in the pathology of Parkinson disease (PD) and is involved in synaptic function, particularly in presynaptic events in dopamine (DA) synapses. Recently, a role for alpha-synuclein in reward and addiction, especially in alcoholism, has been reported. Since PD and alcohol dependence present a strong comorbidity with anxiety disorders, a role for alpha-synuclein in anxiety has been proposed. The aim of the present investigation was to study the involvement of alpha-synuclein in anxiety by testing alpha-synuclein knock out and wild type mice in three different emotionality tests: the open field, the elevated plus maze and the light-dark box. Alpha-synuclein knock out mice and wild type controls displayed consistently similar emotionality profiles in all the tests, suggesting a lack of involvement of alpha-synuclein in unconditioned anxiety in mice.