ProSAAS-derived peptides are regulated by cocaine and are required for sensitization to the locomotor effects of cocaine

Iryna Berezniuk, Ramona M. Rodriguiz, Michael L. Zee, David J. Marcus, John Pintar, Daniel J. Morgan, William C. Wetsel, Lloyd D. Fricker

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


To identify neuropeptides that are regulated by cocaine, we used a quantitative peptidomic technique to examine the relative levels of neuropeptides in several regions of mouse brain following daily intraperitoneal administration of 10 mg/kg cocaine or saline for 7 days. A total of 102 distinct peptides were identified in one or more of the following brain regions: nucleus accumbens, caudate putamen, frontal cortex, and ventral tegmental area. None of the peptides detected in the caudate putamen or frontal cortex were altered by cocaine administration. Three peptides in the nucleus accumbens and seven peptides in the ventral tegmental area were significantly decreased in cocaine-treated mice. Five of these ten peptides are derived from proSAAS, a secretory pathway protein and neuropeptide precursor. To investigate whether proSAAS peptides contribute to the physiological effects of psychostimulants, we examined acute responses to cocaine and amphetamine in the open field with wild-type (WT) and proSAAS knockout (KO) mice. Locomotion was stimulated more robustly in the WT compared to mutant mice for both psychostimulants. Behavioral sensitization to amphetamine was not maintained in proSAAS KO mice and these mutants failed to sensitize to cocaine. To determine whether the rewarding effects of cocaine were altered, mice were tested in conditioned place preference (CPP). Both WT and proSAAS KO mice showed dose-dependent CPP to cocaine that was not distinguished by genotype. Taken together, these results suggest that proSAAS-derived peptides contribute differentially to the behavioral sensitization to psychostimulants, while the rewarding effects of cocaine appear intact in mice lacking proSAAS. (Figure presented.).

Original languageEnglish (US)
Pages (from-to)268-281
Number of pages14
JournalJournal of Neurochemistry
Issue number3
StatePublished - Nov 2017


  • drug abuse
  • neuropeptide
  • peptidomics
  • proteomics

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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