TY - JOUR
T1 - Comparative peptidomics analysis of neural adaptations in rats repeatedly exposed to amphetamine
AU - Romanova, Elena V.
AU - Lee, Ji Eun
AU - Kelleher, Neil L.
AU - Sweedler, Jonathan V.
AU - Gulley, Joshua M.
PY - 2012/11
Y1 - 2012/11
N2 - Repeated exposure to amphetamine (AMPH) induces long-lasting behavioral changes, referred to as sensitization, that are accompanied by various neuroadaptations in the brain. To investigate the chemical changes that occur during behavioral sensitization, we applied a comparative proteomics approach to screen for neuropeptide changes in a rodent model of AMPH-induced sensitization. By measuring peptide profiles with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and comparing signal intensities using principal component analysis and variance statistics, subsets of peptides are found with significant differences in the dorsal striatum, nucleus accumbens, and medial prefrontal cortex of AMPH-sensitized male Sprague-Dawley rats. These biomarker peptides, identified in follow-up analyses using liquid chromatography and tandem mass spectrometry, suggest that behavioral sensitization to AMPH is associated with complex chemical adaptations that regulate energy/metabolism, neurotransmission, apoptosis, neuroprotection, and neuritogenesis, as well as cytoskeleton integrity and neuronal morphology. Our data contribute to a growing number of reports showing that in addition to the mesolimbic dopamine system, which is the best known signaling pathway involved with reinforcing the effect of psychostimulants, concomitant chemical changes in other pathways and in neuronal organization may play a part in the overall effect of chronic AMPH exposure on behavior.
AB - Repeated exposure to amphetamine (AMPH) induces long-lasting behavioral changes, referred to as sensitization, that are accompanied by various neuroadaptations in the brain. To investigate the chemical changes that occur during behavioral sensitization, we applied a comparative proteomics approach to screen for neuropeptide changes in a rodent model of AMPH-induced sensitization. By measuring peptide profiles with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and comparing signal intensities using principal component analysis and variance statistics, subsets of peptides are found with significant differences in the dorsal striatum, nucleus accumbens, and medial prefrontal cortex of AMPH-sensitized male Sprague-Dawley rats. These biomarker peptides, identified in follow-up analyses using liquid chromatography and tandem mass spectrometry, suggest that behavioral sensitization to AMPH is associated with complex chemical adaptations that regulate energy/metabolism, neurotransmission, apoptosis, neuroprotection, and neuritogenesis, as well as cytoskeleton integrity and neuronal morphology. Our data contribute to a growing number of reports showing that in addition to the mesolimbic dopamine system, which is the best known signaling pathway involved with reinforcing the effect of psychostimulants, concomitant chemical changes in other pathways and in neuronal organization may play a part in the overall effect of chronic AMPH exposure on behavior.
KW - addiction
KW - mass spectrometry
KW - neurochemical adaptation
KW - peptidomics
KW - principal component analysis
KW - proteo-mics
UR - http://www.scopus.com/inward/record.url?scp=84867064628&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867064628&partnerID=8YFLogxK
U2 - 10.1111/j.1471-4159.2012.07912.x
DO - 10.1111/j.1471-4159.2012.07912.x
M3 - Article
C2 - 22860605
AN - SCOPUS:84867064628
SN - 0022-3042
VL - 123
SP - 276
EP - 287
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 2
ER -