Cocaine-Induced Remodeling of the Rat Brain Peptidome: Quantitative Mass Spectrometry Reveals Anatomically Specific Patterns of Cocaine-Regulated Peptide Changes

Overview

Journal ACS Chem Neurosci

Publisher American Chemical Society

Date 2025 Jan 15

PMID 39810605

Authors

Gaoyuan Lu

Fengfei Ma

Pingli Wei

Min Ma

Vu Ngoc Huong Tran

Brian A Baldo

Lingjun Li

Affiliations

Soon will be listed here.

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.

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