Effect of Combined Methamphetamine and Oxycodone Use on the Synaptic Proteome in an In Vitro Model of Polysubstance Use

Authors

Daniel Meyer, University of Nebraska Medical Center
Pranavi Athota, University of Nebraska Medical Center
Austin Gowen, University of Nebraska Medical CenterFollow
Nghi M. Nguyen, University of Nebraska Medical Center
Victoria L. Schaal, University of Nebraska Medical CenterFollow
Sowmya V. Yelamanchili, University of Nebraska Medical CenterFollow
Gurudutt Pendyala, University of Nebraska Medical Center, OmahaFollow

Document Type

Article

Journal Title

Genes

Publication Date

2022

Volume

13

Abstract

Polysubstance use (PSU) generally involves the simultaneous use of an opioid along with a stimulant. In recent years, this problem has escalated into a nationwide epidemic. Understanding the mechanisms and effects underlying the interaction between these drugs is essential for the development of treatments for those suffering from addiction. Currently, the effect of PSU on synapses-critical points of contact between neurons-remains poorly understood. Using an in vitro model of primary neurons, we examined the combined effects of the psychostimulant methamphetamine (METH) and the prescription opioid oxycodone (oxy) on the synaptic proteome using quantitative mass-spectrometry-based proteomics. A further ClueGO analysis and Ingenuity Pathway Analysis (IPA) indicated the dysregulation of several molecular functions, biological processes, and pathways associated with neural plasticity and structural development. We identified one key synaptic protein, Striatin-1, which plays a vital role in many of these processes and functions, to be downregulated following METH+oxy treatment. This downregulation of Striatin-1 was further validated by Western blot. Overall, the present study indicates several damaging effects of the combined use of METH and oxy on neural function and warrants further detailed investigation into mechanisms contributing to synaptic dysfunction.

MeSH Headings

Methamphetamine, Oxycodone, Proteome, Analgesics, Opioid, Central Nervous System Stimulants

DOI Link

10.3390/genes13101816

ISSN

2073-4425

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Meyer, Daniel; Athota, Pranavi; Gowen, Austin; Nguyen, Nghi M.; Schaal, Victoria L.; Yelamanchili, Sowmya V.; and Pendyala, Gurudutt, "Effect of Combined Methamphetamine and Oxycodone Use on the Synaptic Proteome in an In Vitro Model of Polysubstance Use" (2022). Journal Articles: Anesthesiology. 15.
https://digitalcommons.unmc.edu/com_anesth_articles/15