Effect of Combined Methamphetamine and Oxycodone Use on the Synaptic Proteome in an
methamphetamine
oxycodone
polysubstance use
speedballing
striatin-1
Journal
Genes
ISSN: 2073-4425
Titre abrégé: Genes (Basel)
Pays: Switzerland
ID NLM: 101551097
Informations de publication
Date de publication:
08 10 2022
08 10 2022
Historique:
received:
15
09
2022
revised:
04
10
2022
accepted:
06
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
29
10
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36292701
pii: genes13101816
doi: 10.3390/genes13101816
pmc: PMC9601452
pii:
doi:
Substances chimiques
Methamphetamine
44RAL3456C
Oxycodone
CD35PMG570
Proteome
0
Analgesics, Opioid
0
Central Nervous System Stimulants
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDA NIH HHS
ID : R21 DA046284
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA049577
Pays : United States
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