# DUSP5 Downregulation in Nucleus Accumbens Core Correlates with Cocaine-Induced Maladaptive Synaptic Plasticity

## TL;DR

This study explores how reduced DUSP5 in a brain region called the nucleus accumbens core is linked to harmful changes in brain connections caused by cocaine use.

## Contribution

The study is the first to investigate the role of DUSP5 in cocaine-induced synaptic plasticity and addiction.

## Key findings

- DUSP5 downregulation correlates with cocaine-induced maladaptive synaptic plasticity in the nucleus accumbens core.
- DUSP5 and its signaling pathways may be key mechanisms in substance use disorders.
- Findings suggest DUSP5 could be a target for therapeutic interventions in addiction.

## 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.