DUSP5 Downregulation in Nucleus Accumbens Core Correlates with Cocaine-Induced Maladaptive Synaptic Plasticity. Cells 2025 Dec 23;15(1)
Date
01/09/2026Pubmed ID
41511316Pubmed Central ID
PMC12785552DOI
10.3390/cells15010032Scopus ID
2-s2.0-105027055097 (requires institutional sign-in at Scopus site)Abstract
The United States is currently facing a drug overdose epidemic. The nucleus accumbens core (NAcore), a brain region critical for reward and aversion behaviors, undergoes structural and functional synaptic adaptations in response to chronic drug exposure. However, the molecular mechanisms underlying these adaptations remain poorly understood. In this study, we investigate the role of dual-specificity phosphatase 5 (DUSP5), a phosphatase known to deactivate extracellular signal-regulated kinase (ERK), in cocaine-induced neuroplasticity. While prior research has linked other DUSP family members to various drugs of abuse, the specific role of DUSP5 in cocaine addiction remains unexplored. We hypothesized that lack of DUSP5 contributes to cocaine-induced maladaptive synaptic plasticity in NAcore. To test this, we employed a rat cocaine self-administration model and molecular analyses and mined publicly available single-cell RNA sequencing data from cocaine-treated NAcore. Our findings reveal a role for DUSP5 in cocaine-related synaptic and behavioral adaptations, highlighting DUSP5 and DUSP5-associated signaling pathways as potential mechanisms underlying substance use disorders and as candidates for therapeutic intervention.
Author List
Taborda-Bejarano JP, Meyerink M, Crans DC, Ramchandran R, Garcia-Keller CAuthors
Constanza Garcia Keller PhD Assistant Professor in the Pharmacology and Toxicology department at Medical College of WisconsinRamani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCocaine
Cocaine-Related Disorders
Down-Regulation
Dual-Specificity Phosphatases
Male
Neuronal Plasticity
Nucleus Accumbens
Rats
Rats, Sprague-Dawley
Self Administration
Signal Transduction
