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Distinct proteomic profiles of amphetamine self-administration transitional states

The Pharmacogenomics Journal volume 5, pages 203–214 (2005)Cite this article

Abstract

In the rat, continuous access to d-amphetamine (d-AMPH) leads to lengthy bouts of self-administration, voluntary abstinence, and relapse to self-administration. Previous studies have revealed that the progression from psychostimulant self-administration to abstinence to relapse is mediated in part by the ventral hippocampus. Stimulation of the ventral subiculum (vSub) during voluntary abstinence from d-AMPH self-administration reinstates self-administration and increases nucleus accumbens (NAc) dopamine efflux. Quantitative proteomic examination of the hippocampus from rats naïve to amphetamine, during a self-administration session ‘Binge’, during voluntarily abstinence ‘Abstinent’, and after reinstatement of self-administration ‘Relapse’, revealed a differential proteomic state during abstinence. Actin- and cytoskeletal-related proteins were over-represented in the changes occurring during abstinence and suggest a decrease in actin filament polymerization. These changes may underlie alterations in neuronal tone during abstinence that could affect both neurotransmission and behavior. These data provide the first classification of addiction-related behaviors based on clustering of quantitative proteomic measurements.

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Abbreviations

d-AMPH:

d-amphetamine

DA:

dopamine

NAc:

nucleus accumbens

IVSA:

intravenous self-administration

vSub:

ventral subiculum

2-DIGE:

two-dimensional difference gel electrophoresis

MALDI-ToF/ToF:

matrix-assisted laser desorption ionization time-of-flight-time-of-flight tandem mass spectrometry

PCA:

Principal Component Analysis

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Acknowledgements

This work was supported by NIH Grants DA015945 (to WMF), DA013830-03S1 (to SGA), and CIHR Grant FRN:36372 (to AGP). NIH Grant DA013772 to Scott E Hemby (Wake Forest University School of Medicine) provided generous financial support and scientific infrastructure.

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Authors and Affiliations

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

    W M Freeman

  2. Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada

    K Brebner & A G Phillips

  3. Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    S G Amara

  4. Microchemical & Proteomics Facility, Emory University School of Medicine, Atlanta, GA, USA

    M S Reed & J Pohl

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  1. W M Freeman
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Correspondence to W M Freeman.

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Supplementary Information accompanies the paper on the The Pharmacogenomics Journal website (http://www.nature.com/tpj).

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Freeman, W., Brebner, K., Amara, S. et al. Distinct proteomic profiles of amphetamine self-administration transitional states. Pharmacogenomics J 5, 203–214 (2005). https://doi.org/10.1038/sj.tpj.6500309

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