D2 neurons activation, leading to disinhibition of the excitatory circuit they project upon.25 Indeed, the KOR JNJ-67953964 was found to increase VTA activation relative to placebo during reward anticipation, highlighting a potential therapeutic mechanism by which KOR is thought to release inhibition on D2 dopaminergic projections. The group receiving JNJ-67953964 showed reduced anhedonic symptoms relative to controls.24 That this gene and brain tissue emerged from hypothesis-free GWAS and TWAS tissue enrichment is a remarkable finding with respect to known biology, and points to the potential value of other novel findings from this kind of research.
