Scientists have discovered a mechanism that helps to explain resilience to stress, vulnerability to depression and how antidepressants work. The new findings, in the reward circuit of mouse and human brains, have spurred a high tech dragnet for compounds that boost the action of a key gene regulator there, called deltaFosB. Triggering deltaFosB, which is depleted in post-mortem brains of depressed patients, protected mice from developing a depression-like syndrome following chronic social stress.