Dopamine release and dopamine-related gene expression in the amygdala are modulated by the gastrin-releasing peptide in opposite directions during stress-enhanced fear learning and extinction

Fear extinction, crucial for survival, involves a decrease in fear responses after threat removal. Deficits in extinction can lead to exaggerated fear or PTSD. This study investigates the role of gastrin-releasing peptide (GRP) in dopamine's function during fear extinction. Using GRP knockout (*Grp*) mice, researchers found enhanced fear memory in a stress-enhanced fear learning (SEFL) paradigm. In vivo fiber photometry revealed increased basolateral amygdala (BLA) dopaminergic binding during fear conditioning and extinction in *Grp* mice. Optogenetics and electrophysiology showed increased VTA-BLA connectivity. RNA-seq and qPCR demonstrated downregulation of dopamine-related genes in the BLA of *Grp* mice after SEFL memory recall. These findings highlight GRP's role in regulating dopamine function during stress-enhanced fear processing and identify *Grp* as a regulator of dopaminergic control of fear extinction.

Yoshikazu Morishita, Ileana Fuentes, Sofia Gonzalez-Salinas, John Favate, Jennifer Mejaes, Ko Zushida, Akinori Nishi, Charles Hevi, Noriko Goldsmith, Steve Buyske, Stephanie E. Sillivan, Courtney A. Miller, Eric R. Kandel, Shusaku Uchida, Premal Shah, Juan Marcos Alarcon, David J. Barker, Gleb P. Shumyatsky