Cocaine abuse elevates alpha-synuclein and dopamine transporter levels in the human striatum

Direct protein interactions between the dopamine transporter and a-synuclein demonstrate that dopamine uptake function is modulated by a-synuclein. We report here that chronic cocaine abuse results in an increase in a-synuclein expression in the human striatum. Immunoblot analysis in the ventral putamen showed that a-synuclein protein was increased in striatal synaptosomes from cocaine users compared with age-matched drug-free controls. [H-3]-Dopamine transporter uptake was increased in parallel with 2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane binding to the dopamine transporter. The increase in a-synuclein protein was more marked in the ventromedial sectors of the striatum than in the dorsal caudate nucleus. These results demonstrate concomitant regulation of a-synuclein and dopamine transporter binding and function in human striatal synaptic terminals isolated from cocaine abusers. Overexpression of a-synuclein may play a role in cocaine-induced plasticity and regulation of dopamine synaptic tone.