ER stress in D1-MSNs mediates cocaine-induced behavioral plasticity <i>via</i> the ATF4-SPTLC1 axis.

ABSTRACT:

Background

Cocaine-induced endoplasmic reticulum (ER) stress has been increasingly recognized, but its neuronal specificity and functional significance remain unclear. Because the ER is also a major site for lipid and sphingolipid biosynthesis, cocaine-triggered ER stress may influence metabolic pathways linked to cellular stress signaling. Here, we sought to define the cell-type specificity and downstream consequences of cocaine-induced ER stress in the nucleus accumbens (NAc).

Methods

We combined cocaine administration with ultrastructural analysis of ER morphology, immunohistochemical and molecular profiling of ER stress pathways, and assays of sphingolipid biosynthesis in the NAc. We also evaluated the effects of pharmacological inhibition of ER stress and sphingolipid s

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC12685851 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature