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The AAPS Journal

, Volume 12, Issue 3, pp 443–454 | Cite as

Mass Spectrometry Screening Reveals Peptides Modulated Differentially in the Medial Prefrontal Cortex of Rats with Disparate Initial Sensitivity to Cocaine

Research Article Theme: Fishing for the Hidden Proteome in Health and Disease: Focus on Drug Abuse

Abstract

To better understand why certain individuals are more vulnerable to cocaine abuse and addiction, we identify peptide markers associated with individual variation in sensitivity to the behavioral effects of cocaine. Previous studies in rats show that low, compared to high, cocaine responders are more sensitive to cocaine-induced behavioral plasticity (sensitization), exhibit enhanced conditioning to cocaine’s rewarding effects, and are more motivated to self administer cocaine. In the current study, we combine matrix-assisted laser desorption/ionization mass spectrometry with multivariate statistical methods to analyze tissue extracts from rat dorsal striatum, nucleus accumbens, and medial prefrontal cortex (mPFC) to examine trends in peptide changes that coincide with behavioral phenotype. Peptide profiles of these three regions from individual animals were characterized via mass spectrometry. Resulting mass peaks that were statistically different between these groups were identified using principal component analysis. The mass peaks were then identified in pooled samples via multistage liquid chromatography mass spectrometry. A total of 74 peptides from 28 proteins were sequenced from defined brain regions. Statistically significant changes in peak intensities for seven peptides were found in the mPFC of rats given a single injection of 10 mg/kg cocaine, with low cocaine responders showing ∼2-fold increase in peak intensities for the acetylated N terminus peptides of stathmin and Hint 1, as well as truncated ATP synthase. These results suggest that distinct peptide profiles in the mPFC are associated with individuals that exhibit reduced sensitivity to the behavioral effects of cocaine.

Key words

addiction biomarkers MALDI-TOF peptidomics principle component analysis 

Notes

Acknowledgments

The project described was supported by Award Numbers DA018310 and DA017940 from the National Institute on Drug Abuse (NIDA). The content is solely the responsibility of the authors and does not necessarily represent the official views of NIDA or the National Institutes of Health. The authors thank Jessica Stanis for technical assistance.

Supplementary material

12248_2010_9204_MOESM1_ESM.pdf (70 kb)
ESM 1 (PDF 69 kb)

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Copyright information

© American Association of Pharmaceutical Scientists 2010

Authors and Affiliations

  1. 1.Department of Chemistry and the Beckman InstituteUniversity of Illinois at Urbana-ChampaignUrbanaUSA
  2. 2.Department of PsychologyUniversity of Illinois at Urbana-ChampaignChampaignUSA
  3. 3.Neuroscience ProgramUniversity of Illinois at Urbana-ChampaignUrbanaUSA

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