Differential peptidomics assessment of strain and age differences in mice in response to acute cocaine administration

Elena V. Romanova, Stanislav S. Rubakhin, John R. Ossyra, Jonathan A. Zombeck, Michael R. Nosek, Jonathan V. Sweedler, Justin S. Rhodes

Research output: Contribution to journalArticlepeer-review


Neurochemical differences in the hypothalamic-pituitary axis between individuals and between ages may contribute to differential susceptibility to cocaine abuse. This study measured peptide levels in the pituitary gland (Pit) and lateral hypothalamus (LH) in adolescent (age 30 days) and adult (age 65 days) mice from four standard inbred strains, FVB/NJ, DBA/2J, C57BL/6J, and BALB/cByJ, which have previously been characterized for acute locomotor responses to cocaine. Individual peptide profiles were analyzed using mass spectrometric profiling and principal component analysis. Sequences of assigned peptides were verified by tandem mass spectrometry. Principal component analysis classified all strains according to their distinct peptide profiles in Pit samples from adolescent mice, but not adults. Select pro-opiomelanocortin-derived peptides were significantly higher in adolescent BALB/cByJ and DBA/2J mice than in FVB/NJ or C57BL/6J mice. A subset of peptides in the LH, but not in the Pit, was altered by cocaine in adolescents. A 15 mg/kg dose of cocaine induced greater peptide alterations than a 30 mg/kg dose, particularly in FVB/NJ animals, with larger differences in adolescents than adults. Neuropeptides in the LH affected by acute cocaine administration included pro-opiomelanocortin-, myelin basic protein-, and glutamate transporter-derived peptides. The observed peptide differences could contribute to differential behavioral sensitivity to cocaine among strains and ages.

Original languageEnglish (US)
Pages (from-to)1038-1048
Number of pages11
JournalJournal of Neurochemistry
Issue number5
StatePublished - Dec 1 2015


  • adolescent
  • cocaine
  • label-free quantitation
  • matrix-assisted laser desorption ionization MS
  • peptidomics
  • principal component analysis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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