Abstract
Methamphetamine is a widely abused, highly addictive drug. Regulation of synaptic proteins within the brain’s reward pathway modulates addiction behaviours, the progression of drug addiction and long-term changes in brain structure and function that result from drug use. Therefore, using large scale proteomics studies we aim to identify global protein expression changes within the dorsal striatum, a key brain region involved in the modulation of addiction. We performed LC-MS/MS analyses on rat striatal synaptosomes following 30 days of methamphetamine self-administration (2 hours/day) and 14 days abstinence. We identified a total of 84 differentially-expressed proteins with known roles in neuroprotection, neuroplasticity, cell cytoskeleton, energy regulation and synaptic vesicles. We identify significant expression changes in stress-induced phosphoprotein and tubulin polymerisation-promoting protein, which have not previously been associated with addiction. In addition, we confirm the role of amphiphysin and phosphatidylethanolamine binding protein in addiction. This approach has provided new insight into the effects of methamphetamine self-administration on synaptic protein expression in a key brain region associated with addiction, showing a large set of differentially-expressed proteins that persist into abstinence. The mass spectrometry proteomics data are available via ProteomeXchange with identifier PXD001443.
Highlights
Methamphetamine is an addictive psychostimulant drug of abuse, with an estimated global annual prevalence of 0.7% and reports of increasing use [1], heightening the need for better understanding of long-term changes in the brain following repeated use
This study is the first to report the use of MS-based proteomics to examine changes in synaptic protein abundance in the dorsal striatum following methamphetamine self-administration in doi:10.1371/journal.pone.0139829.g002
The methamphetamine self-administration model employed in this proteomics study identified changes that suggest a combination of cell stress with synaptic plasticity and neuroadaptation
Summary
Methamphetamine is an addictive psychostimulant drug of abuse, with an estimated global annual prevalence of 0.7% and reports of increasing use [1], heightening the need for better understanding of long-term changes in the brain following repeated use. Many studies use experimenter-administered methamphetamine “binge” treatments that deliver between 10–40 mg/kg to experimental animals in a single day [4,5]. Rat Methamphetamine Self-Administration Proteomics consistently report reduced dopamine, serotonin, dopamine transporter, vesicular monoamine transporter binding and increased glial fibrillary acidic protein following binge regimens in rats, mice and monkeys [3]. Many of these changes occur in the striatum and can persist longer than 6 months [5]
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