Original Article

Molecular Psychiatry (2007) 12, 55–73. doi:10.1038/sj.mp.4001914; published online 31 October 2006

Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims

N Tannu1, D C Mash2 and S E Hemby1

  1. 1Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA
  2. 2Department of Neurology, University of Miami School of Medicine, Miami, FL, USA

Correspondence: Dr SE Hemby, Medical Center Boulevard, Wake Forest University-Bowman Gray School of Medicine, Winston-Salem, NC 27154, USA. E-mail: shemby@wfubmc.edu

Received 26 May 2006; Revised 1 August 2006; Accepted 21 August 2006; Published online 31 October 2006.

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Abstract

Chronic cocaine use in humans and animal models is known to lead to pronounced alterations in neuronal function in the nucleus accumbens (NAc), a brain region associated with drug reinforcement. Two-dimensional gel electrophoresis was used to compare protein alterations in the NAc between cocaine overdose (COD) victims (n=10) and controls (n=10). Following image normalization, spots with significantly differential image intensities (P<0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser desorption ionization-time of flight-time of flight. A total of 1407 spots were found to be present in a minimum of five subjects per group and the intensity of 18 spots was found to be differentially abundant between the groups, leading to positive identification of 15 proteins by peptide mass fingerprinting (PMF). Of an additional 37 protein spots that were constitutively expressed, 32 proteins were positively identified by PMF. Increased proteins in COD included beta-tubulin, liprin-alpha3 and neuronal enolase, whereas decreased proteins included parvalbumin, ATP synthase beta-chain and peroxiredoxin 2. The present data provide a preliminary protein profile of COD, suggesting the involvement of novel proteins and pathways in the expression of this complex disease. Additional studies are warranted to further characterize alterations in the differentially regulated proteins. Understanding the coordinated involvement of multiple proteins in cocaine abuse provides insight into the molecular basis of the disease and offers new targets for pharmacotherapeutic intervention for drug abuse-related disorders.

Keywords:

human, post-mortem, mass spectrometry, 2-D fluorescence difference gel electrophoresis, synaptic signaling