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

Neuroreport. 2005 Sep 8;16(13):1489-93. doi: 10.1097/


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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptation, Physiological / drug effects
  • Chronic Disease
  • Cocaine-Related Disorders / metabolism*
  • Corpus Striatum / metabolism*
  • Dopamine / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Homeostasis / drug effects
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Membrane Transport Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Presynaptic Terminals / metabolism
  • Synucleins
  • alpha-Synuclein


  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SNCA protein, human
  • Synucleins
  • alpha-Synuclein
  • Dopamine