Research Article

Persistent proteomic alterations in the medial prefrontal cortex with abstinence from cocaine self-administration

  1. Melinda E. Lull1,
  2. Mandi S. Erwin1,
  3. Drake Morgan2,
  4. David C. S. Roberts3,
  5. Kent E. Vrana1,†,
  6. Willard M. Freeman Dr.1,4,†,*

Article first published online: 17 MAR 2009

DOI: 10.1002/prca.200800055

Issue

PROTEOMICS - Clinical Applications

PROTEOMICS - Clinical Applications

Special Issue: Focus on Analysis of Drug Effects and Actions

Volume 3, Issue 4, pages 462–472, No. 4 April 2009

Additional Information

How to Cite

Lull, M. E., Erwin, M. S., Morgan, D., Roberts, D. C. S., Vrana, K. E. and Freeman, W. M. (2009), Persistent proteomic alterations in the medial prefrontal cortex with abstinence from cocaine self-administration. Prot. Clin. Appl., 3: 462–472. doi: 10.1002/prca.200800055

Author Information

  1. 1

    Department of Pharmacology, Penn State College of Medicine, Hershey, PA, USA

  2. 2

    Department of Psychiatry, University of Florida, Bainsville, FL, USA

  3. 3

    Department of Physiology & Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA

  4. 4

    Functional Genomics Facility, Penn State College of Medicine, Hershey, PA, USA

  1. †

    These authors contributed equally to this study.

*Department of Pharmacology, R130, Penn State College of Medicine, 500 University Drive, P.O. Box 850, Hershey, PA 17033-0850, USA Fax: +1-717-531-5013

  1. †

    These authors contributed equally to this study.

Publication History

  1. Issue published online: 30 MAR 2009
  2. Article first published online: 17 MAR 2009
  3. Manuscript Received: 19 FEB 2008

Funded by

  • Unknown funding agency. Grant Numbers: R01DA013770-08, F31-DA02281902, R01 DA14030, K01DA13957

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Keywords:

  • Cocaine;
  • Medial prefrontal cortex;
  • Proteomics;
  • Self-administration;
  • Withdrawal

Abstract

Neuroproteomic studies of drug abuse offer the potential for a systems-level understanding of addiction. Understanding cocaine-responsive alterations in brain protein expression that persist even with extended abstinence may provide insight into relapse liability. In the current study, protein changes in the medial prefrontal cortex of cocaine self-administering rats following 1 and 100 days of enforced abstinence were quantified by 2-D DIGE. We have previously reported increased drug-seeking and drug-taking, as well as mRNA and epigenetic changes in this model even after 100 days of enforced abstinence. A number of statistically significant changes in proteins relating to synapse function and neuronal remodeling were evident, including neurofilament medium and Hsp73, which increased at 1 day of abstinence, but returned to normal levels following 100 days of abstinence. Dynamin-1 and synaptosome-associated protein 25 kDa (SNAP-25) were unchanged at 1 day of abstinence, but were significantly decreased after 100 days. These data demonstrate that while some protein changes return to normal levels following enforced cocaine abstinence, a number remain or become altered after long periods, up to 100 days, of cocaine abstinence. Those protein expression changes that do not reset to pre-cocaine exposure levels may contribute to the persistent relapse potential that occurs in response to cocaine abstinence.

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