Cocaine-Induced Remodeling of the Rat Brain Peptidome: Quantitative Mass Spectrometry Reveals Anatomically Specific Patterns of Cocaine-Regulated Peptide Changes
Year: 2024
Type: article
Abstract: Addiction to psychostimulants, including cocaine, causes widespread morbidity and mortality and is a major threat to global public health. Currently, no pharmacotherapies can successfully treat psychostimulant addiction. The neuroactive effects of cocaine and other psychostimulants have been studied extensively with respect to their modulation of monoamine systems (particularly dopamine); effects on neuropeptide systems have received less attention. Here, we employed mass spectrometry (MS) methods to characterize cocaine-induced peptidomic changes in the rat brain. Label-free peptidomic analysis using liquid chromatography coupled with tandem MS (LC-MS/MS) was used to describe the dynamic changes of endogenous peptides in five brain regions (nucleus accumbens, dorsal striatum, prefrontal cortex, amygdala, and hypothalamus) following an acute systemic cocaine challenge. The improved sensitivity and specificity of this method, coupled with quantitative assessment, enabled the identification of 1376 peptides derived from 89 protein precursors. Our data reveal marked, region-specific changes in peptide levels in the brain induced by acute cocaine exposure, with peptides in the cholecystokinin and melanin-concentrating hormone families being significantly affected. These findings offer new insights into the region-specific effects of cocaine and could pave the way for developing new therapies to treat substance use disorders and related psychiatric conditions.
Source: ACS Chemical Neuroscience
Institution: University of Wisconsin–Madison
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Funders: National Science Foundation, Wisconsin Alumni Research Foundation, University of Wisconsin-Madison, National Institutes of Health, Office of the Vice Chancellor for Research and Graduate Education, University of Wisconsin-Madison, National Institute on Aging, National Institute on Drug Abuse, NIH Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, Division of Graduate Education, National Center for Research Resources, Division of Chemistry
Awards: Acquisition of a High-Field Dual Source FTICR-MS for Pharmaceutical Research, G1803960457, G2075862466, G2118924489, G2388130288, G3055837027, Leveraging Ion Mobility and High Resolution Mass Spectrometry to Probe Neuropeptide Modifications in Environmental Stress, G555161754, G6359499187, G6634682943, Acquisition of a High Resolution High Speed MALDI Mass Spectrometer for Biomedical Research at UW-Madison, Acquisition of a Dual-Source, High-Performance, Ion Mobility, Quadrupole Time-of-Flight Mass Spectrometry System for Biomedical Research at UW-Madison, G822836364, G891322577, G9000127380, G9000197343, G9000231773, G932152812, Probing Protein Structural Changes in Alzheimers Disease
OpenAlex ID: W4405949397