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

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