Identification and validation of central amygdala FGFR1 as a therapeutic target for alcohol use disorder using single nucleus sequencing in rat

We used cell-specific transcriptomics to dissect the central amygdala (CeA) of rats that continued drinking alcohol despite punishment—a hallmark of compulsive-like behavior. We found profound transcriptional changes in PKCδ+ neurons, with FGFR1 emerging as a central upstream regulator.

Silencing FgfR1 in these neurons significantly reduced compulsive-like alcohol self-administration, positioning FGFR1 signaling as a promising therapeutic target—especially given the availability of FDA-approved inhibitors. We also uncovered major transcriptional shifts in Calcrl+/Drd2+ neurons, suggesting a broader CeA network reorganization that may contribute to compulsive-like self-administration. Together, these findings identify distinct CeA circuits driving addiction vulnerability, and open new avenues for targeted intervention.