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.

Original languageEnglish (US)
Pages (from-to)443-454
Number of pages12
JournalAAPS Journal
Volume12
Issue number3
DOIs
StatePublished - Sep 1 2010

Fingerprint

Mass Screening
Prefrontal Cortex
Cocaine
Mass Spectrometry
Peptides
Cocaine-Related Disorders
Stathmin
Tissue Extracts
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Nucleus Accumbens
Principal Component Analysis
Liquid Chromatography
Adenosine Triphosphate
Phenotype
Injections
Brain

Keywords

  • addiction
  • biomarkers
  • MALDI-TOF
  • peptidomics
  • principle component analysis

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

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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.",
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author = "Romanova, {Elena V.} and Lee, {Ji Eun} and Kelleher, {Neil L.} and Sweedler, {Jonathan V.} and Gulley, {Joshua M.}",
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