5-HT6R-ATR-primary cilia network supports morphine-related memory extinction in the medial prefrontal cortex.

ABSTRACT: Drug addiction involves pathological learning and memory with serious personal and societal effects. Primary cilia on the cell surface are crucial for signal transduction. The 5-HT6R, highly localized in primary cilia, is linked to cognitive and emotional disorders, but its role in morphine-related reward memory is unclear. Using a morphine-induced conditioned place preference (CPP) model, we found that 5-HT6R in the medial prefrontal cortex was selectively downregulated during early extinction, but unchanged in CPP establishment or reinstatement. Knockdown of 5-HT6R accelerated extinction, while overexpression delayed it. These effects required intact cilia, as cilia shortening or IFT88 knockdown promoted extinction. Mechanistically, ATR was identified as a 5-HT6R-binding protein that reg

SUBMITTER: Liu J 

PROVIDER: S-EPMC12395986 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature